Variant chr3-19896759-A-AAC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_144715.4(EFHB):c.1651_1652dupGT(p.Arg552fs) variant causes a frameshift change. The variant allele was found at a frequency of 0.000817 in 1,614,032 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Uncertain significance (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.00069 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00083 ( 3 hom. )

Consequence

EFHB
NM_144715.4 frameshift

Scores

Not classified

Clinical Significance

Uncertain significance no assertion criteria provided U:2

Conservation

PhyloP100: 3.94

Variant links:

Genes affected

EFHB (HGNC:26330): (EF-hand domain family member B) Enables calcium ion sensor activity. Involved in negative regulation of protein binding activity; regulation of calcineurin-NFAT signaling cascade; and regulation of store-operated calcium entry. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

EFHB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFHB	NM_144715.4 link	c.1651_1652dupGT	p.Arg552fs	frameshift_variant	9/13	ENST00000295824.14	NP_653316.3	Q8N7U6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFHB	ENST00000295824.14 link	c.1651_1652dupGT	p.Arg552fs	frameshift_variant	9/13	1	NM_144715.4	ENSP00000295824.9		Q8N7U6-1

Frequencies

GnomAD3 genomes

AF:

0.000690

AC:

105

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00327

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:

0.000661

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000605

AC:

152

AN:

251162

Hom.:

AF XY:

0.000523

AC XY:

AN XY:

135726

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00156

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000775

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.000830

AC:

1213

AN:

1461706

Hom.:

Cov.:

AF XY:

0.000725

AC XY:

527

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.00152

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000994

Gnomad4 OTH exome

AF:

0.000547

GnomAD4 genome

AF:

0.000689

AC:

105

AN:

152326

Hom.:

Cov.:

AF XY:

0.000631

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000661

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000248

Hom.:

Bravo

AF:

0.000820

EpiCase

AF:

0.000763

EpiControl

AF:

0.000711

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Uncertain:2

Uncertain significance, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Uncertain significance, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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