rs61741725

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_013275.6(ANKRD11):c.3822C>T(p.Ala1274=) 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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 ClinVar 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 Lovd as [Benign].

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/exons	MANE	Protein
ANKRD11	NM_013275.6 linkuse as main transcript	c.3822C>T	p.Ala1274=	synonymous_variant	9/13	ENST00000301030.10	NP_037407.4
ANKRD11	NM_001256182.2 linkuse as main transcript	c.3822C>T	p.Ala1274=	synonymous_variant	10/14		NP_001243111.1
ANKRD11	NM_001256183.2 linkuse as main transcript	c.3822C>T	p.Ala1274=	synonymous_variant	9/13		NP_001243112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD11	ENST00000301030.10 linkuse as main transcript	c.3822C>T	p.Ala1274=	synonymous_variant	9/13	5	NM_013275.6	ENSP00000301030	P1

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

GnomAD3 exomes

AF:

0.0400

AC:

10054

AN:

251352

Hom.:

370

AF XY:

0.0392

AC XY:

5331

AN XY:

135876

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 SAS exome

AF:

0.00960

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

Gnomad4 AFR exome

AF:

0.00624

Gnomad4 AMR exome

AF:

0.0292

Gnomad4 ASJ exome

AF:

0.0113

Gnomad4 EAS exome

AF:

0.0624

Gnomad4 SAS exome

AF:

0.0115

Gnomad4 FIN exome

AF:

0.122

Gnomad4 NFE exome

AF:

0.0395

Gnomad4 OTH exome

AF:

0.0351

GnomAD4 genome

AF:

0.0337

AC:

5117

AN:

151988

Hom.:

150

Cov.:

AF XY:

0.0374

AC XY:

2781

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.00731

Gnomad4 AMR

AF:

0.0244

Gnomad4 ASJ

AF:

0.00980

Gnomad4 EAS

AF:

0.0637

Gnomad4 SAS

AF:

0.0156

Gnomad4 FIN

AF:

0.129

Gnomad4 NFE

AF:

0.0381

Gnomad4 OTH

AF:

0.0251

Alfa

AF:

0.0274

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 22, 2015	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. -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 28, 2017	- -

KBG syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 19, 2016

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.053

DANN

Benign

0.40

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.2

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over