rs773314113

Positions:

• chr10-90918980-CAAAATA-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2 BP6_Very_Strong

The NM_014391.3(ANKRD1):​c.346-14_346-9del 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 0.0000398 in 1,305,016 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00088 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: ANKRD1 NM_014391.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.67

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.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 10-90918980-CAAAATA-C is Benign according to our data. Variant chr10-90918980-CAAAATA-C is described in ClinVar as [Likely_benign]. Clinvar id is 201657.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-90918980-CAAAATA-C is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD1	NM_014391.3	c.346-14_346-9del		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.346-14_346-9del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_014391.3	ENSP00000360762	P1

Frequencies

GnomAD3 genomes AF: 0.000883 AC: 39 AN: 44146 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00496

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00112

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000639

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 13 AN: 1260892 Hom.: 0 AF XY: 0.00000789 AC XY: 5 AN XY: 633438

Gnomad4 AFR exome AF: 0.000287

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000900

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000429

Gnomad4 NFE exome AF: 0.00000208

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.000884 AC: 39 AN: 44124 Hom.: 0 Cov.: 0 AF XY: 0.000910 AC XY: 19 AN XY: 20882

Gnomad4 AFR AF: 0.00496

Gnomad4 AMR AF: 0.00113

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000643

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000240 Hom.: 0

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Cardiomyopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 06, 2013

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

ANKRD1-related dilated cardiomyopathy Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 21, 2023

- -

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: rs773314113; hg19: chr10-92678737;