10-90912291-TAAAAAAAAAAAAAAAAAA-TAAAAAAAAAAA

Variant names:

• chr10-90912291-TAAAAAAA-T
• rs71025330
• NM_014391.3:c.*568_*574delTTTTTTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_014391.3(ANKRD1):​c.*568_*574delTTTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 70,612 control chromosomes in the GnomAD database, including 1,790 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.24 (1790 hom., cov: 0)
  • Exomes 𝑓: 0.12 (0 hom.)
• Consequence: ANKRD1 NM_014391.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63
• Publications: 1 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.365 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.*568_*574delTTTTTTT		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.*568_*574delTTTTTTT		3_prime_UTR	Exon 9 of 9	ENSP00000360762.3	Q15327
	ANKRD1	ENST00000869698.1		c.*568_*574delTTTTTTT		3_prime_UTR	Exon 8 of 8	ENSP00000539757.1
	ANKRD1	ENST00000945870.1		c.*568_*574delTTTTTTT		3_prime_UTR	Exon 8 of 8	ENSP00000615929.1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 17120 AN: 70362 Hom.: 1787 Cov.: 0

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.307

GnomAD4 exome AF: 0.120 AC: 28 AN: 234 Hom.: 0 AF XY: 0.104 AC XY: 11 AN XY: 106

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.160 AC: 8 AN: 50

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.167 AC: 1 AN: 6

South Asian (SAS) AF: 0.143 AC: 2 AN: 14

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.106 AC: 17 AN: 160

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.243 AC: 17124 AN: 70378 Hom.: 1790 Cov.: 0 AF XY: 0.253 AC XY: 7995 AN XY: 31610

African (AFR) AF: 0.323 AC: 6972 AN: 21608

American (AMR) AF: 0.345 AC: 1818 AN: 5262

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 366 AN: 1990

East Asian (EAS) AF: 0.353 AC: 840 AN: 2378

South Asian (SAS) AF: 0.390 AC: 629 AN: 1612

European-Finnish (FIN) AF: 0.301 AC: 276 AN: 916

Middle Eastern (MID) AF: 0.318 AC: 28 AN: 88

European-Non Finnish (NFE) AF: 0.167 AC: 5851 AN: 35062

Other (OTH) AF: 0.307 AC: 271 AN: 884

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs71025330; hg19: chr10-92672048;