Variant 1-63532754-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032437.4(EFCAB7):c.484A>G(p.Lys162Glu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000582 in 1,597,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

EFCAB7
NM_032437.4 missense, splice_region

Scores

Splicing: ADA: 0.001010

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.62

Variant links:

Genes affected

EFCAB7 (HGNC:29379): (EF-hand calcium binding domain 7) Predicted to enable calcium ion binding activity. Predicted to be involved in positive regulation of protein import into nucleus; positive regulation of protein localization to ciliary membrane; and positive regulation of transcription by RNA polymerase II. Predicted to be located in ciliary membrane. Predicted to be extrinsic component of membrane. Predicted to be part of plasma membrane protein complex. [provided by Alliance of Genome Resources, Apr 2022]

EFCAB7 links:

EFCAB7 (HGNC:):

EFCAB7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.049802065).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFCAB7	NM_032437.4 linkuse as main transcript	c.484A>G	p.Lys162Glu	missense_variant, splice_region_variant	4/14	ENST00000371088.5	NP_115813.2	A8K855-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFCAB7	ENST00000371088.5 linkuse as main transcript	c.484A>G	p.Lys162Glu	missense_variant, splice_region_variant	4/14	1	NM_032437.4	ENSP00000360129.4		A8K855-1
ITGB3BP	ENST00000478138.1 linkuse as main transcript	n.198-3568T>C		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000989

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

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

GnomAD3 exomes

AF:

0.0000887

AC:

AN:

236672

Hom.:

AF XY:

0.0000546

AC XY:

AN XY:

128298

show subpopulations

Gnomad AFR exome

AF:

0.00108

Gnomad AMR exome

AF:

0.0000336

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000727

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000913

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000353

AC:

AN:

1444994

Hom.:

Cov.:

AF XY:

0.0000320

AC XY:

AN XY:

718966

show subpopulations

Gnomad4 AFR exome

AF:

0.000743

Gnomad4 AMR exome

AF:

0.0000501

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000121

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000271

Gnomad4 OTH exome

AF:

0.000351

GnomAD4 genome

AF:

0.000276

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.000986

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000279

Hom.:

Bravo

AF:

0.000249

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000906

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3476

EpiCase

AF:

0.00

EpiControl

AF:

0.0000597

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 15, 2023

The c.484A>G (p.K162E) alteration is located in exon 4 (coding exon 3) of the EFCAB7 gene. This alteration results from a A to G substitution at nucleotide position 484, causing the lysine (K) at amino acid position 162 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.018

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.020

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.83

M_CAP

Benign

0.0041

MetaRNN

Benign

0.050

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.64

PrimateAI

Uncertain

0.50

PROVEAN

Benign

0.37

REVEL

Benign

0.072

Sift

Benign

0.62

Sift4G

Benign

0.56

Polyphen

0.089

Vest4

0.34

MVP

0.31

MPC

0.23

ClinPred

0.030

GERP RS

4.5

Varity_R

0.30

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0010

dbscSNV1_RF

Benign

0.078

SpliceAI score (max)

0.010

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