Genetic Variant ANKRD1:c.*572_*574dupTTT (chr10-90912291-T-TAAA) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_014391.3(ANKRD1):c.*572_*574dupTTT 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 0.022 ( 113 hom., cov: 0)

Exomes 𝑓: 0.043 ( 0 hom. )

Consequence

ANKRD1
NM_014391.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.12

Publications

1 publications found

Variant links:

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

ANKRD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0225 (1580/70334) while in subpopulation AFR AF = 0.025 (539/21564). AF 95% confidence interval is 0.0233. There are 113 homozygotes in GnomAd4. There are 701 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High AC in GnomAd4 at 1580 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.572_574dupTTT		3_prime_UTR	Exon 9 of 9	NP_055206.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANKRD1	ENST00000371697.4	TSL:1 MANE Select	c.572_574dupTTT	3_prime_UTR	Exon 9 of 9	ENSP00000360762.3	Q15327
ANKRD1	ENST00000869698.1		c.572_574dupTTT	3_prime_UTR	Exon 8 of 8	ENSP00000539757.1
ANKRD1	ENST00000945870.1		c.572_574dupTTT	3_prime_UTR	Exon 8 of 8	ENSP00000615929.1

Frequencies

GnomAD3 genomes

AF:

0.0225

AC:

1581

AN:

70320

Hom.:

113

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0250

Gnomad AMI

AF:

0.0310

Gnomad AMR

AF:

0.0154

Gnomad ASJ

AF:

0.0353

Gnomad EAS

AF:

0.00378

Gnomad SAS

AF:

0.0185

Gnomad FIN

AF:

0.00766

Gnomad MID

AF:

0.0521

Gnomad NFE

AF:

0.0227

Gnomad OTH

AF:

0.0293

GnomAD4 exome

AF:

0.0435

AC:

AN:

230

Hom.:

Cov.:

AF XY:

0.0377

AC XY:

AN XY:

106

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AF:

0.0400

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.0714

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0449

AC:

AN:

156

Other (OTH)

AF:

0.00

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000676748), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.350

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0225

AC:

1580

AN:

70334

Hom.:

113

Cov.:

AF XY:

0.0222

AC XY:

701

AN XY:

31608

show subpopulations

African (AFR)

AF:

0.0250

AC:

539

AN:

21564

American (AMR)

AF:

0.0154

AC:

AN:

5254

Ashkenazi Jewish (ASJ)

AF:

0.0353

AC:

AN:

1982

East Asian (EAS)

AF:

0.00379

AC:

AN:

2376

South Asian (SAS)

AF:

0.0180

AC:

AN:

1614

European-Finnish (FIN)

AF:

0.00766

AC:

AN:

914

Middle Eastern (MID)

AF:

0.0568

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0227

AC:

796

AN:

35078

Other (OTH)

AF:

0.0294

AC:

AN:

884

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

112

167

223

279

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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10-90912291-TAAAAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over