16-89282720-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_013275.6(ANKRD11):c.3822C>T(p.Ala1274Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.039 in 1,613,692 control chromosomes in the GnomAD database, including 1,594 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 150 hom., cov: 32)

Exomes 𝑓: 0.040 ( 1444 hom. )

Consequence

ANKRD11
NM_013275.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -4.71

Publications

6 publications found

Variant links:

Genes affected

ANKRD11 (HGNC:21316): (ankyrin repeat domain containing 11) This locus encodes an ankryin repeat domain-containing protein. The encoded protein inhibits ligand-dependent activation of transcription. Mutations in this gene have been associated with KBG syndrome, which is characterized by macrodontia, distinctive craniofacial features, short stature, skeletal anomalies, global developmental delay, seizures and intellectual disability. Alternatively spliced transcript variants have been described. Related pseudogenes exist on chromosomes 2 and X. [provided by RefSeq, Jan 2012]

ANKRD11 Gene-Disease associations (from GenCC):

KBG syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P, Illumina, ClinGen
congenital heart defects, multiple types
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ANKRD11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 16-89282720-G-A is Benign according to our data. Variant chr16-89282720-G-A is described in CliVar as Benign. Clinvar id is 380366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89282720-G-A is described in CliVar as Benign. Clinvar id is 380366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89282720-G-A is described in CliVar as Benign. Clinvar id is 380366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89282720-G-A is described in CliVar as Benign. Clinvar id is 380366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89282720-G-A is described in CliVar as Benign. Clinvar id is 380366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89282720-G-A is described in CliVar as Benign. Clinvar id is 380366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89282720-G-A is described in CliVar as Benign. Clinvar id is 380366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89282720-G-A is described in CliVar as Benign. Clinvar id is 380366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.71 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD11	NM_013275.6 link	c.3822C>T	p.Ala1274Ala	synonymous_variant	Exon 9 of 13	ENST00000301030.10	NP_037407.4	Q6UB99
ANKRD11	NM_001256182.2 link	c.3822C>T	p.Ala1274Ala	synonymous_variant	Exon 10 of 14		NP_001243111.1	Q6UB99
ANKRD11	NM_001256183.2 link	c.3822C>T	p.Ala1274Ala	synonymous_variant	Exon 9 of 13		NP_001243112.1	Q6UB99

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD11	ENST00000301030.10 link	c.3822C>T	p.Ala1274Ala	synonymous_variant	Exon 9 of 13	5	NM_013275.6	ENSP00000301030.4		Q6UB99

Frequencies

GnomAD3 genomes

AF:

0.0337

AC:

5116

AN:

151870

Hom.:

150

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00733

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0245

Gnomad ASJ

AF:

0.00980

Gnomad EAS

AF:

0.0634

Gnomad SAS

AF:

0.0154

Gnomad FIN

AF:

0.129

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0380

Gnomad OTH

AF:

0.0254

GnomAD2 exomes

AF:

0.0400

AC:

10054

AN:

251352

AF XY:

0.0392

show subpopulations

Gnomad AFR exome

AF:

0.00739

Gnomad AMR exome

AF:

0.0285

Gnomad ASJ exome

AF:

0.0103

Gnomad EAS exome

AF:

0.0664

Gnomad FIN exome

AF:

0.126

Gnomad NFE exome

AF:

0.0382

Gnomad OTH exome

AF:

0.0427

GnomAD4 exome

AF:

0.0396

AC:

57821

AN:

1461704

Hom.:

1444

Cov.:

AF XY:

0.0385

AC XY:

28025

AN XY:

727164

show subpopulations

African (AFR)

AF:

0.00624

AC:

209

AN:

33480

American (AMR)

AF:

0.0292

AC:

1308

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0113

AC:

295

AN:

26136

East Asian (EAS)

AF:

0.0624

AC:

2479

AN:

39700

South Asian (SAS)

AF:

0.0115

AC:

996

AN:

86254

European-Finnish (FIN)

AF:

0.122

AC:

6470

AN:

53244

Middle Eastern (MID)

AF:

0.00729

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0395

AC:

43904

AN:

1112008

Other (OTH)

AF:

0.0351

AC:

2118

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

3460

6920

10379

13839

17299

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1684

3368

5052

6736

8420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0337

AC:

5117

AN:

151988

Hom.:

150

Cov.:

AF XY:

0.0374

AC XY:

2781

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.00731

AC:

303

AN:

41438

American (AMR)

AF:

0.0244

AC:

373

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00980

AC:

AN:

3468

East Asian (EAS)

AF:

0.0637

AC:

329

AN:

5162

South Asian (SAS)

AF:

0.0156

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.129

AC:

1361

AN:

10528

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0381

AC:

2587

AN:

67988

Other (OTH)

AF:

0.0251

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

243

487

730

974

1217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0281

Hom.:

Bravo

AF:

0.0251

Asia WGS

AF:

0.0400

AC:

140

AN:

3478

EpiCase

AF:

0.0307

EpiControl

AF:

0.0293

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Feb 16, 2024

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 22, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

KBG syndrome

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Apr 19, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.053

(source)

DANN

Benign

0.40

PhyloP100

-4.7

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.2

Mutation Taster

=94/6

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over