10-90912807-T-C

Variant names:

• chr10-90912807-T-C
• rs3939
• NM_014391.3:c.*59A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014391.3(ANKRD1):​c.*59A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 1,458,726 control chromosomes in the GnomAD database, including 161,971 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (12678 hom., cov: 32)
  • Exomes 𝑓: 0.47 (149293 hom.)
• Consequence: ANKRD1 NM_014391.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.638
• Publications: 18 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 10-90912807-T-C is Benign according to our data. Variant chr10-90912807-T-C is described in ClinVar as Benign. ClinVar VariationId is 301603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

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.*59A>G		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.*59A>G		3_prime_UTR	Exon 9 of 9	ENSP00000360762.3	Q15327
	ANKRD1	ENST00000869698.1		c.*59A>G		3_prime_UTR	Exon 8 of 8	ENSP00000539757.1
	ANKRD1	ENST00000945870.1		c.*59A>G		3_prime_UTR	Exon 8 of 8	ENSP00000615929.1

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59725 AN: 152034 Hom.: 12682 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.414

GnomAD4 exome AF: 0.473 AC: 617617 AN: 1306574 Hom.: 149293 Cov.: 18 AF XY: 0.471 AC XY: 309912 AN XY: 658412

African (AFR) AF: 0.195 AC: 5912 AN: 30380

American (AMR) AF: 0.490 AC: 21792 AN: 44494

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 11907 AN: 25112

East Asian (EAS) AF: 0.360 AC: 14019 AN: 38920

South Asian (SAS) AF: 0.402 AC: 33327 AN: 82926

European-Finnish (FIN) AF: 0.461 AC: 24472 AN: 53082

Middle Eastern (MID) AF: 0.439 AC: 2407 AN: 5482

European-Non Finnish (NFE) AF: 0.493 AC: 478552 AN: 970962

Other (OTH) AF: 0.457 AC: 25229 AN: 55216

GnomAD4 genome AF: 0.393 AC: 59732 AN: 152152 Hom.: 12678 Cov.: 32 AF XY: 0.393 AC XY: 29246 AN XY: 74384

African (AFR) AF: 0.209 AC: 8658 AN: 41524

American (AMR) AF: 0.463 AC: 7083 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 1599 AN: 3470

East Asian (EAS) AF: 0.363 AC: 1885 AN: 5188

South Asian (SAS) AF: 0.409 AC: 1971 AN: 4824

European-Finnish (FIN) AF: 0.454 AC: 4802 AN: 10578

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.475 AC: 32248 AN: 67954

Other (OTH) AF: 0.414 AC: 873 AN: 2110

Alfa AF: 0.454 Hom.: 25695

Bravo AF: 0.385

Asia WGS AF: 0.371 AC: 1294 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Primary dilated cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.5
DANN	Benign	0.63
PhyloP100		-0.64
Mutation Taster		=100/0	polymorphism (auto)

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: rs3939; hg19: chr10-92672564; COSMIC: COSV65467427; COSMIC: COSV65467427;