10-90912651-GTAAA-G

Variant names:

• chr10-90912651-GTAAA-G
• rs143761686
• NM_014391.3:c.*211_*214delTTTA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_014391.3(ANKRD1):​c.*211_*214delTTTA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00569 in 499,142 control chromosomes in the GnomAD database, including 70 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (54 hom., cov: 31)
  • Exomes 𝑓: 0.0018 (16 hom.)
• Consequence: ANKRD1 NM_014391.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.82
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 10-90912651-GTAAA-G is Benign according to our data. Variant chr10-90912651-GTAAA-G is described in ClinVar as Likely_benign. ClinVar VariationId is 301602.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0145 (2208/152270) while in subpopulation AFR AF = 0.0506 (2103/41540). AF 95% confidence interval is 0.0488. There are 54 homozygotes in GnomAd4. There are 1023 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2208 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.*211_*214delTTTA		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.*211_*214delTTTA		3_prime_UTR	Exon 9 of 9	ENSP00000360762.3	Q15327
	ANKRD1	ENST00000869698.1		c.*211_*214delTTTA		3_prime_UTR	Exon 8 of 8	ENSP00000539757.1
	ANKRD1	ENST00000945870.1		c.*211_*214delTTTA		3_prime_UTR	Exon 8 of 8	ENSP00000615929.1

Frequencies

GnomAD3 genomes AF: 0.0145 AC: 2200 AN: 152152 Hom.: 53 Cov.: 31

Gnomad AFR AF: 0.0506

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00537

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00669

GnomAD4 exome AF: 0.00182 AC: 630 AN: 346872 Hom.: 16 AF XY: 0.00156 AC XY: 292 AN XY: 186900

African (AFR) AF: 0.0508 AC: 501 AN: 9862

American (AMR) AF: 0.00250 AC: 41 AN: 16370

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10288

East Asian (EAS) AF: 0.0000475 AC: 1 AN: 21044

South Asian (SAS) AF: 0.0000912 AC: 4 AN: 43860

European-Finnish (FIN) AF: 0.000389 AC: 7 AN: 18018

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1438

European-Non Finnish (NFE) AF: 0.000102 AC: 21 AN: 206824

Other (OTH) AF: 0.00287 AC: 55 AN: 19168

GnomAD4 genome AF: 0.0145 AC: 2208 AN: 152270 Hom.: 54 Cov.: 31 AF XY: 0.0137 AC XY: 1023 AN XY: 74452

African (AFR) AF: 0.0506 AC: 2103 AN: 41540

American (AMR) AF: 0.00536 AC: 82 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68036

Other (OTH) AF: 0.00662 AC: 14 AN: 2116

Alfa AF: 0.0125 Hom.: 6

Bravo AF: 0.0162

Asia WGS AF: 0.00260 AC: 9 AN: 3476

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Dilated Cardiomyopathy, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.8
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: rs143761686; hg19: chr10-92672408;