10-90912500-C-T

Variant names:

• chr10-90912500-C-T
• rs17102330
• NM_014391.3:c.*366G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_014391.3(ANKRD1):​c.*366G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 263,790 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (11 hom., cov: 31)
  • Exomes 𝑓: 0.014 (21 hom.)
• Consequence: ANKRD1 NM_014391.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.20

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 10-90912500-C-T is Benign according to our data. Variant chr10-90912500-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 880084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0107 (1631/152096) while in subpopulation NFE AF= 0.0183 (1246/68002). AF 95% confidence interval is 0.0175. There are 11 homozygotes in gnomad4. There are 713 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD1	NM_014391.3	c.*366G>A		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.*366G>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_014391.3	ENSP00000360762.3

Frequencies

GnomAD3 genomes AF: 0.0107 AC: 1632 AN: 151978 Hom.: 11 Cov.: 31

Gnomad AFR AF: 0.00329

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00583

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00394

Gnomad FIN AF: 0.00785

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0183

Gnomad OTH AF: 0.00766

GnomAD4 exome AF: 0.0144 AC: 1609 AN: 111694 Hom.: 21 Cov.: 0 AF XY: 0.0132 AC XY: 783 AN XY: 59310

Gnomad4 AFR exome AF: 0.00290

Gnomad4 AMR exome AF: 0.00376

Gnomad4 ASJ exome AF: 0.00823

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00471

Gnomad4 FIN exome AF: 0.0141

Gnomad4 NFE exome AF: 0.0199

Gnomad4 OTH exome AF: 0.0144

GnomAD4 genome AF: 0.0107 AC: 1631 AN: 152096 Hom.: 11 Cov.: 31 AF XY: 0.00959 AC XY: 713 AN XY: 74332

Gnomad4 AFR AF: 0.00328

Gnomad4 AMR AF: 0.00582

Gnomad4 ASJ AF: 0.0104

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.00394

Gnomad4 FIN AF: 0.00785

Gnomad4 NFE AF: 0.0183

Gnomad4 OTH AF: 0.00758

Alfa AF: 0.0142 Hom.: 1

Bravo AF: 0.0101

Asia WGS AF: 0.00260 AC: 9 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Primary dilated cardiomyopathy Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.077
DANN	Benign	0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs17102330; hg19: chr10-92672257;