Genetic Variant ANKRD11:c.-60+13446T>G (chr16-89404838-A-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_013275.6(ANKRD11):c.-60+13446T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,184 control chromosomes in the GnomAD database, including 10,831 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.33 ( 10831 hom., cov: 32)

Consequence

ANKRD11
NM_013275.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.132

Publications

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

ANKRD11 links:

LOC128462377 (HGNC:0):

LOC128462377 links:

LOC128462377 (HGNC:):

LOC128462377 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013275.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANKRD11	NM_013275.6	MANE Select	c.-60+13446T>G	intron	N/A	NP_037407.4
LOC128462377	NM_001416403.1	MANE Select	c.9+13446T>G	intron	N/A	NP_001403332.1	A0AAA9YHJ5
ANKRD11	NM_001256182.2		c.-60+13446T>G	intron	N/A	NP_001243111.1	Q6UB99

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANKRD11	ENST00000301030.10	TSL:5 MANE Select	c.-60+13446T>G	intron	N/A	ENSP00000301030.4	Q6UB99
ENSG00000288715	ENST00000711617.1	MANE Select	c.9+13446T>G	intron	N/A	ENSP00000518812.1	A0AAA9YHJ5
ANKRD11	ENST00000378330.7	TSL:1	c.-60+13446T>G	intron	N/A	ENSP00000367581.2	Q6UB99

Frequencies

GnomAD3 genomes

AF:

0.333

AC:

50568

AN:

152066

Hom.:

10833

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0937

Gnomad AMI

AF:

0.535

Gnomad AMR

AF:

0.353

Gnomad ASJ

AF:

0.579

Gnomad EAS

AF:

0.0467

Gnomad SAS

AF:

0.215

Gnomad FIN

AF:

0.352

Gnomad MID

AF:

0.563

Gnomad NFE

AF:

0.481

Gnomad OTH

AF:

0.436

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.332

AC:

50549

AN:

152184

Hom.:

10831

Cov.:

AF XY:

0.322

AC XY:

23976

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.0935

AC:

3887

AN:

41554

American (AMR)

AF:

0.352

AC:

5377

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.579

AC:

2006

AN:

3462

East Asian (EAS)

AF:

0.0466

AC:

242

AN:

5188

South Asian (SAS)

AF:

0.216

AC:

1041

AN:

4828

European-Finnish (FIN)

AF:

0.352

AC:

3725

AN:

10584

Middle Eastern (MID)

AF:

0.551

AC:

162

AN:

294

European-Non Finnish (NFE)

AF:

0.481

AC:

32713

AN:

67976

Other (OTH)

AF:

0.430

AC:

909

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1556

3113

4669

6226

7782

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

478

956

1434

1912

2390

<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:

0.426

Hom.:

44076

Bravo

AF:

0.325

Asia WGS

AF:

0.127

AC:

442

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

(source)

DANN

Benign

0.37

PhyloP100

0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.29

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.29

Position offset: 0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over