rs397517250

Positions:

• chr10-90918981-AAAATAAAT-A
• chr10-90918981-AAAATAAAT-AAAAT
• chr10-90918981-AAAATAAAT-AAAATAAATAAAT
• chr10-90918981-AAAATAAAT-AAAATAAATAAATAAAT

Variant summary

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

The NM_014391.3(ANKRD1):​c.346-17_346-10del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0189 in 1,269,304 control chromosomes in the GnomAD database, including 3,441 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0059 (7 hom., cov: 0)
  • Exomes 𝑓: 0.020 (3434 hom.)
• Consequence: ANKRD1 NM_014391.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 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 10-90918981-AAAATAAAT-A is Benign according to our data. Variant chr10-90918981-AAAATAAAT-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 45631.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=4, Uncertain_significance=1}. Variant chr10-90918981-AAAATAAAT-A is described in Lovd as [Benign].
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD1	NM_014391.3	c.346-17_346-10del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000371697.4	NP_055206.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD1	ENST00000371697.4	c.346-17_346-10del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_014391.3	ENSP00000360762	P1

Frequencies

GnomAD3 genomes AF: 0.00587 AC: 524 AN: 89238 Hom.: 7 Cov.: 0

Gnomad AFR AF: 0.00598

Gnomad AMI AF: 0.00169

Gnomad AMR AF: 0.00343

Gnomad ASJ AF: 0.00316

Gnomad EAS AF: 0.00588

Gnomad SAS AF: 0.00566

Gnomad FIN AF: 0.00638

Gnomad MID AF: 0.00459

Gnomad NFE AF: 0.00666

Gnomad OTH AF: 0.00158

GnomAD4 exome AF: 0.0199 AC: 23458 AN: 1180070 Hom.: 3434 AF XY: 0.0206 AC XY: 12232 AN XY: 592942

Gnomad4 AFR exome AF: 0.134

Gnomad4 AMR exome AF: 0.0713

Gnomad4 ASJ exome AF: 0.0184

Gnomad4 EAS exome AF: 0.0619

Gnomad4 SAS exome AF: 0.0519

Gnomad4 FIN exome AF: 0.0178

Gnomad4 NFE exome AF: 0.0121

Gnomad4 OTH exome AF: 0.0216

GnomAD4 genome AF: 0.00588 AC: 525 AN: 89234 Hom.: 7 Cov.: 0 AF XY: 0.00604 AC XY: 258 AN XY: 42742

Gnomad4 AFR AF: 0.00598

Gnomad4 AMR AF: 0.00343

Gnomad4 ASJ AF: 0.00316

Gnomad4 EAS AF: 0.00619

Gnomad4 SAS AF: 0.00567

Gnomad4 FIN AF: 0.00638

Gnomad4 NFE AF: 0.00666

Gnomad4 OTH AF: 0.00158

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:7

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Congenital total pulmonary venous return anomaly Benign:3

Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Oct 11, 2017	- -
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	Oct 26, 2016	- -

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 20, 2013	The c.346-17_346-10del variant in ANKRD1 has not been reported in the literature nor previously identified by our laboratory. This variant is located in a rep etitive region in intron 3 that contains several other common deletions and has been detected in 2/100 control chromosomes tested by our laboratory. Based on t he overall evidence for variants affecting this region and its frequency in cont rols this variant is likely benign. -

Dilated Cardiomyopathy, Dominant Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Cardiomyopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 08, 2013

The variant is found in DCM panel(s). -

ANKRD1-related dilated cardiomyopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 19, 2024

- -

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;