rs72003210

Variant names:

• chr10-90918983-AATAAATAAATATATATAT-A
• rs72003210
• NM_014391.3:c.346-29_346-12delATATATATATTTATTTAT

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• Publications: 2 publications found

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]

ANKRD1 Gene-Disease associations (from GenCC):

• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• congenital heart disease

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• dilated cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• hypertrophic cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 301605.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014391.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD1	NM_014391.3	MANE Select	c.346-29_346-12delATATATATATTTATTTAT		intron	N/A	NP_055206.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD1	ENST00000371697.4	TSL:1 MANE Select	c.346-29_346-12delATATATATATTTATTTAT		intron	N/A	ENSP00000360762.3	Q15327
	ANKRD1	ENST00000869698.1		c.346-29_346-12delATATATATATTTATTTAT		intron	N/A	ENSP00000539757.1
	ANKRD1	ENST00000945870.1		c.346-29_346-12delATATATATATTTATTTAT		intron	N/A	ENSP00000615929.1

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

GnomAD2 exomes AF: 0.560 AC: 119603 AN: 213642 AF XY: 0.556

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 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

African (AFR) AF: 0.506 AC: 8270 AN: 16352

American (AMR) AF: 0.677 AC: 24888 AN: 36752

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 13276 AN: 23262

East Asian (EAS) AF: 0.597 AC: 16635 AN: 27848

South Asian (SAS) AF: 0.595 AC: 41170 AN: 69174

European-Finnish (FIN) AF: 0.595 AC: 26906 AN: 45254

Middle Eastern (MID) AF: 0.605 AC: 2878 AN: 4754

European-Non Finnish (NFE) AF: 0.593 AC: 591403 AN: 997272

Other (OTH) AF: 0.592 AC: 30552 AN: 51632

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

African (AFR) AF: 0.274 AC: 8751 AN: 31942

American (AMR) AF: 0.501 AC: 7100 AN: 14174

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1609 AN: 3400

East Asian (EAS) AF: 0.425 AC: 1911 AN: 4494

South Asian (SAS) AF: 0.462 AC: 2000 AN: 4328

European-Finnish (FIN) AF: 0.555 AC: 5039 AN: 9080

Middle Eastern (MID) AF: 0.438 AC: 119 AN: 272

European-Non Finnish (NFE) AF: 0.498 AC: 32558 AN: 65384

Other (OTH) AF: 0.460 AC: 888 AN: 1932

Alfa AF: 0.455 Hom.: 1570

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	2	Congenital total pulmonary venous return anomaly (2)
-	2	-	Dilated Cardiomyopathy, Dominant (2)
-	-	1	ANKRD1-related dilated cardiomyopathy (1)
-	-	1	ANKRD1-related disorder (1)
-	-	1	Cardiovascular phenotype (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs72003210; hg19: chr10-92678740; COSMIC: COSV106063358; COSMIC: COSV106063358;