chr10-90918981-A-AAAAT

Position:

• chr10-90918981-A-AAAAT

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The ENST00000371697.4(ANKRD1):​c.346-13_346-10dupATTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000149 in 1,312,720 control chromosomes in the GnomAD database, including 9 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (8 hom., cov: 18)
  • Exomes 𝑓: 0.000048 (1 hom.)
• Consequence: ANKRD1 ENST00000371697.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.181

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 10-90918981-A-AAAAT is Benign according to our data. Variant chr10-90918981-A-AAAAT is described in ClinVar as [Likely_benign]. Clinvar id is 416999.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD1	NM_014391.3	c.346-13_346-10dupATTT		intron_variant		ENST00000371697.4	NP_055206.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD1	ENST00000371697.4	c.346-13_346-10dupATTT		intron_variant		1	NM_014391.3	ENSP00000360762.3

Frequencies

GnomAD3 genomes AF: 0.00148 AC: 135 AN: 91022 Hom.: 8 Cov.: 18

Gnomad AFR AF: 0.00483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000113

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00235

GnomAD4 exome AF: 0.0000483 AC: 59 AN: 1221698 Hom.: 1 Cov.: 26 AF XY: 0.0000553 AC XY: 34 AN XY: 614710

Gnomad4 AFR exome AF: 0.00214

Gnomad4 AMR exome AF: 0.0000503

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000274

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000748

Gnomad4 OTH exome AF: 0.000159

GnomAD4 genome AF: 0.00149 AC: 136 AN: 91022 Hom.: 8 Cov.: 18 AF XY: 0.00131 AC XY: 57 AN XY: 43546

Gnomad4 AFR AF: 0.00486

Gnomad4 AMR AF: 0.000113

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00235

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

ANKRD1-related dilated cardiomyopathy Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 04, 2024

- -

ANKRD1-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 01, 2019

This variant is classified as likely 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: rs397517250; hg19: chr10-92678738;