Genetic Variant ANKRD1:c.*211_*214delTTTA (chr10-90912651-GTAAA-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_014391.3(ANKRD1):c.*211_*214delTTTA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00569 in 499,142 control chromosomes in the GnomAD database, including 70 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.015 ( 54 hom., cov: 31)

Exomes 𝑓: 0.0018 ( 16 hom. )

Consequence

ANKRD1
NM_014391.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.82

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 10-90912651-GTAAA-G is Benign according to our data. Variant chr10-90912651-GTAAA-G is described in ClinVar as [Likely_benign]. Clinvar id is 301602.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0145 (2208/152270) while in subpopulation AFR AF = 0.0506 (2103/41540). AF 95% confidence interval is 0.0488. There are 54 homozygotes in GnomAd4. There are 1023 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position FAILED quality control check.

BS2

High Homozygotes in GnomAd4 at 54 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD1	NM_014391.3 link	c.211_214delTTTA		3_prime_UTR_variant	Exon 9 of 9	ENST00000371697.4	NP_055206.2	Q15327A0A384NYH5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD1	ENST00000371697 link	c.211_214delTTTA		3_prime_UTR_variant	Exon 9 of 9	1	NM_014391.3	ENSP00000360762.3		Q15327

Frequencies

GnomAD3 genomes

AF:

0.0145

AC:

2200

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0506

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00537

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00669

GnomAD4 exome

AF:

0.00182

AC:

630

AN:

346872

Hom.:

AF XY:

0.00156

AC XY:

292

AN XY:

186900

show subpopulations

Gnomad4 AFR exome

AF:

0.0508

AC:

501

AN:

9862

Gnomad4 AMR exome

AF:

0.00250

AC:

AN:

16370

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

10288

Gnomad4 EAS exome

AF:

0.0000475

AC:

AN:

21044

Gnomad4 SAS exome

AF:

0.0000912

AC:

AN:

43860

Gnomad4 FIN exome

AF:

0.000389

AC:

AN:

18018

Gnomad4 NFE exome

AF:

0.000102

AC:

AN:

206824

Gnomad4 Remaining exome

AF:

0.00287

AC:

AN:

19168

Heterozygous variant carriers

126

158

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

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:

0.0145

AC:

2208

AN:

152270

Hom.:

Cov.:

AF XY:

0.0137

AC XY:

1023

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0506

AC:

0.0506259

AN:

0.0506259

Gnomad4 AMR

AF:

0.00536

AC:

0.00536368

AN:

0.00536368

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.0000943

AC:

0.0000943396

AN:

0.0000943396

Gnomad4 NFE

AF:

0.000118

AC:

0.000117585

AN:

0.000117585

Gnomad4 OTH

AF:

0.00662

AC:

0.00661626

AN:

0.00661626

Heterozygous variant carriers

109

218

326

435

544

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.0125

Hom.:

Bravo

AF:

0.0162

Asia WGS

AF:

0.00260

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Dilated Cardiomyopathy, Dominant

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=100/0

polymorphism

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over