Variant 3-19896743-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000295824.14(EFHB):c.1669A>C(p.Lys557Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00642 in 1,614,022 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0043 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0066 ( 38 hom. )

Consequence

EFHB
ENST00000295824.14 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.72

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 Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007995367).

BP6

Variant 3-19896743-T-G is Benign according to our data. Variant chr3-19896743-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 712993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFHB	NM_144715.4 linkuse as main transcript	c.1669A>C	p.Lys557Gln	missense_variant	9/13	ENST00000295824.14	NP_653316.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFHB	ENST00000295824.14 linkuse as main transcript	c.1669A>C	p.Lys557Gln	missense_variant	9/13	1	NM_144715.4	ENSP00000295824	P2	Q8N7U6-1

Frequencies

GnomAD3 genomes

AF:

0.00427

AC:

650

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.00570

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00675

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00452

AC:

1135

AN:

251172

Hom.:

AF XY:

0.00462

AC XY:

627

AN XY:

135736

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.00304

Gnomad ASJ exome

AF:

0.00298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00389

Gnomad FIN exome

AF:

0.00153

Gnomad NFE exome

AF:

0.00701

Gnomad OTH exome

AF:

0.00473

GnomAD4 exome

AF:

0.00664

AC:

9711

AN:

1461702

Hom.:

Cov.:

AF XY:

0.00659

AC XY:

4790

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.00279

Gnomad4 ASJ exome

AF:

0.00383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00377

Gnomad4 FIN exome

AF:

0.00206

Gnomad4 NFE exome

AF:

0.00777

Gnomad4 OTH exome

AF:

0.00600

GnomAD4 genome

AF:

0.00427

AC:

650

AN:

152320

Hom.:

Cov.:

AF XY:

0.00420

AC XY:

313

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00103

Gnomad4 AMR

AF:

0.00569

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.000941

Gnomad4 NFE

AF:

0.00675

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00607

Hom.:

Bravo

AF:

0.00441

TwinsUK

AF:

0.00728

AC:

ALSPAC

AF:

0.00752

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00744

AC:

ExAC

AF:

0.00428

AC:

520

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00594

EpiControl

AF:

0.00688

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 25, 2017	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.48

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.090

T;.

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.0080

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;.

MutationTaster

Benign

0.99

D;D

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-2.8

D;D

REVEL

Benign

0.12

Sift

Uncertain

0.016

D;D

Sift4G

Uncertain

0.019

D;D

Polyphen

0.91

P;P

Vest4

0.48

MVP

0.62

MPC

0.22

ClinPred

0.018

GERP RS

5.2

Varity_R

0.29

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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