rs58762441

chr10-90918985-TAAATAA-Tchr10-90918985-TAAATAA-TAchr10-90918985-TAAATAA-TAAATAAAATAA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_014391.3(ANKRD1):c.346-19_346-14del 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 0.17 in 301,188 control chromosomes in the GnomAD database, including 4,516 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (2543 hom., cov: 0)
  • Exomes 𝑓: 0.14 (1973 hom.)
• Consequence: ANKRD1 NM_014391.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• 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 -16 ACMG points.

• BP6: Variant 10-90918985-TAAATAA-T is Benign according to our data. Variant chr10-90918985-TAAATAA-T is described in ClinVar as [Benign]. Clinvar id is 45632.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-90918985-TAAATAA-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD1	NM_014391.3	c.346-19_346-14del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000371697.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD1	ENST00000371697.4	c.346-19_346-14del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_014391.3	P1

Frequencies

GnomAD3 genomes AF: 0.273 AC: 17302 AN: 63404 Hom.: 2543 Cov.: 0

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.0385

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.251

GnomAD3 exomes AF: 0.0514 AC: 10913 AN: 212278 Hom.: 2160 AF XY: 0.0495 AC XY: 5726 AN XY: 115692

Gnomad AFR exome AF: 0.183

Gnomad AMR exome AF: 0.0434

Gnomad ASJ exome AF: 0.0311

Gnomad EAS exome AF: 0.112

Gnomad SAS exome AF: 0.0664

Gnomad FIN exome AF: 0.0458

Gnomad NFE exome AF: 0.0297

Gnomad OTH exome AF: 0.0367

GnomAD4 exome AF: 0.143 AC: 34049 AN: 237782 Hom.: 1973 AF XY: 0.144 AC XY: 17244 AN XY: 119524

Gnomad4 AFR exome AF: 0.403

Gnomad4 AMR exome AF: 0.350

Gnomad4 ASJ exome AF: 0.143

Gnomad4 EAS exome AF: 0.339

Gnomad4 SAS exome AF: 0.281

Gnomad4 FIN exome AF: 0.177

Gnomad4 NFE exome AF: 0.0993

Gnomad4 OTH exome AF: 0.172

GnomAD4 genome AF: 0.273 AC: 17302 AN: 63406 Hom.: 2543 Cov.: 0 AF XY: 0.280 AC XY: 8573 AN XY: 30570

Gnomad4 AFR AF: 0.405

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.251

Alfa AF: 0.106 Hom.: 85

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 06, 2013	346-19_346-14del in intron 3 of ANKRD1: This variant is not expected to have cli nical significance because it has been identified in 6% (6/100) of control chrom osomes by our laboratory (LMM unpublished data). In addition, this variant lies within a highly variable region of the intron where multiple deletions of variou s sizes identified in the general population have been observed, suggesting that variation in this region is tolerated. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 17, 2023	- -

Congenital total pulmonary venous return anomaly Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, University Medical Center Utrecht

May 11, 2016

- -

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

Invitae

Feb 01, 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: rs58762441; hg19: chr10-92678742;