10-90912500-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

ANKRD1 Gene-Disease associations (from GenCC):

• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• congenital heart disease

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• dilated cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• hypertrophic cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1631 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014391.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD1	NM_014391.3	MANE Select	c.*366G>A		3_prime_UTR	Exon 9 of 9	NP_055206.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD1	ENST00000371697.4	TSL:1 MANE Select	c.*366G>A		3_prime_UTR	Exon 9 of 9	ENSP00000360762.3	Q15327
	ANKRD1	ENST00000869698.1		c.*366G>A		3_prime_UTR	Exon 8 of 8	ENSP00000539757.1
	ANKRD1	ENST00000945870.1		c.*366G>A		3_prime_UTR	Exon 8 of 8	ENSP00000615929.1

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

African (AFR) AF: 0.00290 AC: 10 AN: 3454

American (AMR) AF: 0.00376 AC: 19 AN: 5056

Ashkenazi Jewish (ASJ) AF: 0.00823 AC: 22 AN: 2672

East Asian (EAS) AF: 0.00 AC: 0 AN: 5646

South Asian (SAS) AF: 0.00471 AC: 83 AN: 17612

European-Finnish (FIN) AF: 0.0141 AC: 66 AN: 4682

Middle Eastern (MID) AF: 0.00930 AC: 4 AN: 430

European-Non Finnish (NFE) AF: 0.0199 AC: 1324 AN: 66536

Other (OTH) AF: 0.0144 AC: 81 AN: 5606

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

African (AFR) AF: 0.00328 AC: 136 AN: 41480

American (AMR) AF: 0.00582 AC: 89 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0104 AC: 36 AN: 3458

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5166

South Asian (SAS) AF: 0.00394 AC: 19 AN: 4820

European-Finnish (FIN) AF: 0.00785 AC: 83 AN: 10570

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0183 AC: 1246 AN: 68002

Other (OTH) AF: 0.00758 AC: 16 AN: 2110

Alfa AF: 0.0142 Hom.: 1

Bravo AF: 0.0101

Asia WGS AF: 0.00260 AC: 9 AN: 3476

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Primary dilated cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.077
DANN	Benign	0.30
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs17102330; hg19: chr10-92672257;