10-90912291-TAAAAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAAAAAAAA

Variant names:

• chr10-90912291-T-TAAAAAA
• rs71025330
• NM_014391.3:c.*569_*574dupTTTTTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_014391.3(ANKRD1):​c.*569_*574dupTTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.020 (106 hom., cov: 0)
  • Exomes 𝑓: 0.0085 (0 hom.)
• Consequence: ANKRD1 NM_014391.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• 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.

• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0199 (1398/70314) while in subpopulation SAS AF = 0.0242 (39/1612). AF 95% confidence interval is 0.0196. There are 106 homozygotes in GnomAd4. There are 633 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1398 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.*569_*574dupTTTTTT		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.*569_*574dupTTTTTT		3_prime_UTR	Exon 9 of 9	ENSP00000360762.3	Q15327
	ANKRD1	ENST00000869698.1		c.*569_*574dupTTTTTT		3_prime_UTR	Exon 8 of 8	ENSP00000539757.1
	ANKRD1	ENST00000945870.1		c.*569_*574dupTTTTTT		3_prime_UTR	Exon 8 of 8	ENSP00000615929.1

Frequencies

GnomAD3 genomes AF: 0.0199 AC: 1399 AN: 70302 Hom.: 106 Cov.: 0

Gnomad AFR AF: 0.0180

Gnomad AMI AF: 0.00345

Gnomad AMR AF: 0.0149

Gnomad ASJ AF: 0.0368

Gnomad EAS AF: 0.0214

Gnomad SAS AF: 0.0241

Gnomad FIN AF: 0.0198

Gnomad MID AF: 0.0104

Gnomad NFE AF: 0.0208

Gnomad OTH AF: 0.0226

GnomAD4 exome AF: 0.00855 AC: 2 AN: 234 Hom.: 0 Cov.: 0 AF XY: 0.0189 AC XY: 2 AN XY: 106

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 50

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 6

South Asian (SAS) AF: 0.00 AC: 0 AN: 14

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

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0125 AC: 2 AN: 160

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

GnomAD4 genome AF: 0.0199 AC: 1398 AN: 70314 Hom.: 106 Cov.: 0 AF XY: 0.0200 AC XY: 633 AN XY: 31582

African (AFR) AF: 0.0179 AC: 387 AN: 21562

American (AMR) AF: 0.0149 AC: 78 AN: 5250

Ashkenazi Jewish (ASJ) AF: 0.0368 AC: 73 AN: 1984

East Asian (EAS) AF: 0.0210 AC: 50 AN: 2376

South Asian (SAS) AF: 0.0242 AC: 39 AN: 1612

European-Finnish (FIN) AF: 0.0198 AC: 18 AN: 910

Middle Eastern (MID) AF: 0.0114 AC: 1 AN: 88

European-Non Finnish (NFE) AF: 0.0208 AC: 730 AN: 35068

Other (OTH) AF: 0.0226 AC: 20 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		-1.1
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;