rs72821356

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.4932G>A(p.Gly1644Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0389 in 1,614,124 control chromosomes in the GnomAD database, including 1,585 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 153 hom., cov: 32)

Exomes 𝑓: 0.039 ( 1432 hom. )

Consequence

ANKRD11
NM_013275.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.863

Publications

7 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=-0.84).

BP6

Variant 16-89281610-C-T is Benign according to our data. Variant chr16-89281610-C-T is described in ClinVar as Benign. ClinVar VariationId is 380367.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.863 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD11	NM_013275.6 link	c.4932G>A	p.Gly1644Gly	synonymous_variant	Exon 9 of 13	ENST00000301030.10	NP_037407.4	Q6UB99
ANKRD11	NM_001256182.2 link	c.4932G>A	p.Gly1644Gly	synonymous_variant	Exon 10 of 14		NP_001243111.1	Q6UB99
ANKRD11	NM_001256183.2 link	c.4932G>A	p.Gly1644Gly	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.4932G>A	p.Gly1644Gly	synonymous_variant	Exon 9 of 13	5	NM_013275.6	ENSP00000301030.4		Q6UB99

Frequencies

GnomAD3 genomes

AF:

0.0337

AC:

5119

AN:

152118

Hom.:

153

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00722

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0246

Gnomad ASJ

AF:

0.00922

Gnomad EAS

AF:

0.0620

Gnomad SAS

AF:

0.0157

Gnomad FIN

AF:

0.130

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0380

Gnomad OTH

AF:

0.0253

GnomAD2 exomes

AF:

0.0401

AC:

10063

AN:

250712

AF XY:

0.0393

show subpopulations

Gnomad AFR exome

AF:

0.00750

Gnomad AMR exome

AF:

0.0284

Gnomad ASJ exome

AF:

0.0102

Gnomad EAS exome

AF:

0.0665

Gnomad FIN exome

AF:

0.127

Gnomad NFE exome

AF:

0.0382

Gnomad OTH exome

AF:

0.0426

GnomAD4 exome

AF:

0.0395

AC:

57700

AN:

1461888

Hom.:

1432

Cov.:

AF XY:

0.0385

AC XY:

27975

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.00621

AC:

208

AN:

33480

American (AMR)

AF:

0.0292

AC:

1305

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0110

AC:

287

AN:

26136

East Asian (EAS)

AF:

0.0624

AC:

2478

AN:

39700

South Asian (SAS)

AF:

0.0116

AC:

998

AN:

86258

European-Finnish (FIN)

AF:

0.122

AC:

6518

AN:

53414

Middle Eastern (MID)

AF:

0.00728

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0393

AC:

43746

AN:

1112012

Other (OTH)

AF:

0.0351

AC:

2118

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

3946

7891

11837

15782

19728

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1678

3356

5034

6712

8390

<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:

0.0336

AC:

5120

AN:

152236

Hom.:

153

Cov.:

AF XY:

0.0375

AC XY:

2788

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.00719

AC:

299

AN:

41562

American (AMR)

AF:

0.0245

AC:

375

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00922

AC:

AN:

3472

East Asian (EAS)

AF:

0.0624

AC:

322

AN:

5164

South Asian (SAS)

AF:

0.0159

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.130

AC:

1374

AN:

10598

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0380

AC:

2586

AN:

67996

Other (OTH)

AF:

0.0251

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

252

504

757

1009

1261

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:

0.0325

Hom.:

Bravo

AF:

0.0251

Asia WGS

AF:

0.0410

AC:

143

AN:

3478

EpiCase

AF:

0.0306

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

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. -

Feb 16, 2024

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

KBG syndrome

Benign:2

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.84

CADD

Benign

0.46

(source)

DANN

Benign

0.20

PhyloP100

-0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

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