10-90912291-TAAAAAAAAA-T

Variant names:

• chr10-90912291-TAAAAAAAAA-T
• rs71025330
• NM_014391.3:c.*566_*574delTTTTTTTTT

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS1_Supporting

The NM_014391.3(ANKRD1):​c.*566_*574delTTTTTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0684 in 234 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.021 (30 hom., cov: 0)
  • Exomes 𝑓: 0.068 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANKRD1 NM_014391.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.63

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 -1 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0684 (16/234) while in subpopulation AMR AF= 0.1 (5/50). AF 95% confidence interval is 0.0394. There are 0 homozygotes in gnomad4_exome. There are 7 alleles in male gnomad4_exome subpopulation. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD1	NM_014391.3	c.*566_*574delTTTTTTTTT		3_prime_UTR_variant	Exon 9 of 9	ENST00000371697.4	NP_055206.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD1	ENST00000371697	c.*566_*574delTTTTTTTTT		3_prime_UTR_variant	Exon 9 of 9	1	NM_014391.3	ENSP00000360762.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1460 AN: 70388 Hom.: 30 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.00885

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.0220

Gnomad ASJ AF: 0.0296

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00617

Gnomad FIN AF: 0.0448

Gnomad MID AF: 0.0313

Gnomad NFE AF: 0.0259

Gnomad OTH AF: 0.0203

GnomAD4 exome AF: 0.0684 AC: 16 AN: 234 Hom.: 0 AF XY: 0.0660 AC XY: 7 AN XY: 106

Gnomad4 AMR exome AF: 0.100

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0714

Gnomad4 NFE exome AF: 0.0625

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0207 AC: 1460 AN: 70402 Hom.: 30 Cov.: 0 AF XY: 0.0201 AC XY: 635 AN XY: 31630

Gnomad4 AFR AF: 0.00889

Gnomad4 AMR AF: 0.0220

Gnomad4 ASJ AF: 0.0296

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00618

Gnomad4 FIN AF: 0.0448

Gnomad4 NFE AF: 0.0259

Gnomad4 OTH AF: 0.0204

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Dilated Cardiomyopathy, Dominant Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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: rs71025330; hg19: chr10-92672048;