rs72003210

Positions:

• chr10-90918983-AATAAATAAATATATATAT-A
• chr10-90918983-AATAAATAAATATATATAT-AATAAATAAATATATATATATAAATAAATATATATAT

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The NM_014391.3(ANKRD1):​c.346-29_346-12delATATATATATTTATTTAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 1,408,210 control chromosomes in the GnomAD database, including 253,135 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.44 (14706 hom., cov: 0)
  • Exomes 𝑓: 0.59 (238429 hom.)
• Consequence: ANKRD1 NM_014391.3 intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 B:7
• Conservation: PhyloP100: 3.19

Genes affected

ANKRD1 (HGNC:15819): (ankyrin repeat domain 1) The protein encoded by this gene is localized to the nucleus of endothelial cells and is induced by IL-1 and TNF-alpha stimulation. Studies in rat cardiomyocytes suggest that this gene functions as a transcription factor. Interactions between this protein and the sarcomeric proteins myopalladin and titin suggest that it may also be involved in the myofibrillar stretch-sensor system. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP6: Variant 10-90918983-AATAAATAAATATATATAT-A is Benign according to our data. Variant chr10-90918983-AATAAATAAATATATATAT-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 301605.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=1, Benign=4}. Variant chr10-90918983-AATAAATAAATATATATAT-A is described in Lovd as [Benign]. Variant chr10-90918983-AATAAATAAATATATATAT-A is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD1	NM_014391.3	c.346-29_346-12delATATATATATTTATTTAT		intron_variant		ENST00000371697.4	NP_055206.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD1	ENST00000371697.4	c.346-29_346-12delATATATATATTTATTTAT		intron_variant		1	NM_014391.3	ENSP00000360762.3

Frequencies

GnomAD3 genomes AF: 0.445 AC: 60452 AN: 135870 Hom.: 14703 Cov.: 0

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.426

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.458

GnomAD3 exomes AF: 0.560 AC: 119603 AN: 213642 Hom.: 36309 AF XY: 0.556 AC XY: 65030 AN XY: 117004

Gnomad AFR exome AF: 0.430

Gnomad AMR exome AF: 0.609

Gnomad ASJ exome AF: 0.527

Gnomad EAS exome AF: 0.543

Gnomad SAS exome AF: 0.515

Gnomad FIN exome AF: 0.562

Gnomad NFE exome AF: 0.574

Gnomad OTH exome AF: 0.564

GnomAD4 exome AF: 0.594 AC: 755978 AN: 1272300 Hom.: 238429 AF XY: 0.592 AC XY: 375536 AN XY: 634102

Gnomad4 AFR exome AF: 0.506

Gnomad4 AMR exome AF: 0.677

Gnomad4 ASJ exome AF: 0.571

Gnomad4 EAS exome AF: 0.597

Gnomad4 SAS exome AF: 0.595

Gnomad4 FIN exome AF: 0.595

Gnomad4 NFE exome AF: 0.593

Gnomad4 OTH exome AF: 0.592

GnomAD4 genome AF: 0.445 AC: 60467 AN: 135910 Hom.: 14706 Cov.: 0 AF XY: 0.450 AC XY: 29624 AN XY: 65904

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.473

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.462

Gnomad4 FIN AF: 0.555

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.460

Alfa AF: 0.455 Hom.: 1570

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2 Benign:7

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Dilated Cardiomyopathy, Dominant Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

Congenital total pulmonary venous return anomaly Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Sep 06, 2016	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Apr 25, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

ANKRD1-related dilated cardiomyopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Cardiovascular phenotype Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 28, 2015

This alteration is classified as likely 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. -

ANKRD1-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 03, 2022

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs72003210; hg19: chr10-92678740;