Genetic Variant ANKRD1:c.*573_*574dupTT (chr10-90912291-T-TAA) – 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.*573_*574dupTT 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 0.029 ( 115 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 = 0.0293 (2057/70296) while in subpopulation AFR AF = 0.0346 (746/21538). AF 95% confidence interval is 0.0326. There are 115 homozygotes in GnomAd4. There are 890 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High AC in GnomAd4 at 2057 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.573_574dupTT		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.573_574dupTT	3_prime_UTR	Exon 9 of 9	ENSP00000360762.3	Q15327
ANKRD1	ENST00000869698.1		c.573_574dupTT	3_prime_UTR	Exon 8 of 8	ENSP00000539757.1
ANKRD1	ENST00000945870.1		c.573_574dupTT	3_prime_UTR	Exon 8 of 8	ENSP00000615929.1

Frequencies

GnomAD3 genomes

AF:

0.0292

AC:

2055

AN:

70282

Hom.:

115

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0346

Gnomad AMI

AF:

0.0190

Gnomad AMR

AF:

0.0158

Gnomad ASJ

AF:

0.0206

Gnomad EAS

AF:

0.0214

Gnomad SAS

AF:

0.0142

Gnomad FIN

AF:

0.0396

Gnomad MID

AF:

0.0208

Gnomad NFE

AF:

0.0299

Gnomad OTH

AF:

0.0169

GnomAD4 exome

AF:

0.0427

AC:

AN:

234

Hom.:

Cov.:

AF XY:

0.0283

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:

0.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0500

AC:

AN:

160

Other (OTH)

AF:

0.00

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000329604), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.385

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:

0.0293

AC:

2057

AN:

70296

Hom.:

115

Cov.:

AF XY:

0.0282

AC XY:

890

AN XY:

31584

show subpopulations

African (AFR)

AF:

0.0346

AC:

746

AN:

21538

American (AMR)

AF:

0.0158

AC:

AN:

5258

Ashkenazi Jewish (ASJ)

AF:

0.0206

AC:

AN:

1990

East Asian (EAS)

AF:

0.0214

AC:

AN:

2378

South Asian (SAS)

AF:

0.0143

AC:

AN:

1612

European-Finnish (FIN)

AF:

0.0396

AC:

AN:

910

Middle Eastern (MID)

AF:

0.0227

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0299

AC:

1049

AN:

35058

Other (OTH)

AF:

0.0170

AC:

AN:

884

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

152

229

305

381

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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-TAAAAAAAAAAAAAAAAAAAA

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