Genetic Variant EFHB:p.Thr382Asn (chr3-19918264-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_144715.4(EFHB):c.1145C>A(p.Thr382Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 29)

Failed GnomAD Quality Control

Consequence

EFHB
NM_144715.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.167

Publications

35 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.065645665).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144715.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFHB	NM_144715.4	MANE Select	c.1145C>A	p.Thr382Asn	missense	Exon 4 of 13	NP_653316.3
	EFHB	NM_001330688.2		c.755C>A	p.Thr252Asn	missense	Exon 6 of 15	NP_001317617.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
EFHB	ENST00000295824.14	TSL:1 MANE Select	c.1145C>A	p.Thr382Asn	missense	Exon 4 of 13	ENSP00000295824.9
EFHB	ENST00000344838.8	TSL:2	c.755C>A	p.Thr252Asn	missense	Exon 6 of 15	ENSP00000342263.4
EFHB	ENST00000440022.1	TSL:5	c.356C>A	p.Thr119Asn	missense	Exon 3 of 7	ENSP00000396778.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151568

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

151568

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74000

African (AFR)

AF:

0.00

AC:

AN:

41250

American (AMR)

AF:

0.00

AC:

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5134

South Asian (SAS)

AF:

0.00

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10476

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67898

Other (OTH)

AF:

0.00

AC:

AN:

2082

Alfa

AF:

0.00

Hom.:

85839

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

6.1

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.00073

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.20

M_CAP

Benign

0.0042

MetaRNN

Benign

0.066

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

PhyloP100

-0.17

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.63

REVEL

Benign

0.017

Sift

Benign

0.47

Sift4G

Benign

0.39

Polyphen

0.0010

Vest4

0.12

MutPred

0.35

Loss of catalytic residue at T382 (P = 0.0174)

MVP

0.29

MPC

0.036

ClinPred

0.091

GERP RS

1.6

Varity_R

0.043

gMVP

0.25

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over