Genetic Variant ANKRD1:c.*565_*574delTTTTTTTTTT (chr10-90912291-TAAAAAAAAAA-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_014391.3(ANKRD1):c.*565_*574delTTTTTTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000552 in 70,644 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., cov: 0)

Exomes 𝑓: 0.034 ( 0 hom. )

Consequence

ANKRD1
NM_014391.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.63

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: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 31 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.565_574delTTTTTTTTTT		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.565_574delTTTTTTTTTT	3_prime_UTR	Exon 9 of 9	ENSP00000360762.3	Q15327
ANKRD1	ENST00000869698.1		c.565_574delTTTTTTTTTT	3_prime_UTR	Exon 8 of 8	ENSP00000539757.1
ANKRD1	ENST00000945870.1		c.565_574delTTTTTTTTTT	3_prime_UTR	Exon 8 of 8	ENSP00000615929.1

Frequencies

GnomAD3 genomes

AF:

0.000440

AC:

AN:

70398

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00139

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000285

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0345

AC:

AN:

232

Hom.:

AF XY:

0.0385

AC XY:

AN XY:

104

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:

0.0417

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:

0.0250

AC:

AN:

160

Other (OTH)

AF:

0.250

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000139124), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.394

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:

0.000440

AC:

AN:

70412

Hom.:

Cov.:

AF XY:

0.000474

AC XY:

AN XY:

31638

show subpopulations

African (AFR)

AF:

0.00139

AC:

AN:

21600

American (AMR)

AF:

0.00

AC:

AN:

5268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1990

East Asian (EAS)

AF:

0.00

AC:

AN:

2380

South Asian (SAS)

AF:

0.00

AC:

AN:

1618

European-Finnish (FIN)

AF:

0.00

AC:

AN:

914

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0000285

AC:

AN:

35090

Other (OTH)

AF:

0.00

AC:

AN:

884

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.583

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.6

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-TAAAAAAAA

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