Genetic Variant NM_001143943.1:c.392G>A (chr1-245121938-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001143943.1(EFCAB2):c.392G>A(p.Arg131His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00669 in 413,916 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0067 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0067 ( 10 hom. )

Consequence

EFCAB2
NM_001143943.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.31

Variant links:

Genes affected

EFCAB2 (HGNC:28166): (EF-hand calcium binding domain 2) The gene encodes a protein that contains two EF-hand calcium-binding domains although its function has yet to be determined. Alternatively spliced transcripts have been observed. [provided by RefSeq, Mar 2014]

EFCAB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006601095).

BP6

Variant 1-245121938-G-A is Benign according to our data. Variant chr1-245121938-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3770774.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
EFCAB2	NM_001143943.1 link	c.392G>A	p.Arg131His	missense_variant	Exon 7 of 7	NP_001137415.1	Q5VUJ9-3
EFCAB2	XM_017002539.2 link	c.590-2756G>A		intron_variant	Intron 8 of 8	XP_016858028.2
EFCAB2	XM_017002540.2 link	c.590-2767G>A		intron_variant	Intron 8 of 8	XP_016858029.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
EFCAB2	ENST00000447569.6 link	c.392G>A	p.Arg131His	missense_variant	Exon 7 of 7	2	ENSP00000408661.2	Q5VUJ9-3
EFCAB2	ENST00000366522.6 link	n.941G>A		non_coding_transcript_exon_variant	Exon 8 of 8	2
EFCAB2	ENST00000479923.1 link	n.138G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2
EFCAB2	ENST00000487845.5 link	n.336G>A		non_coding_transcript_exon_variant	Exon 6 of 6	2

Frequencies

GnomAD3 genomes

AF:

0.00668

AC:

1007

AN:

150644

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00449

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00544

Gnomad ASJ

AF:

0.00722

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00231

Gnomad FIN

AF:

0.00222

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00991

Gnomad OTH

AF:

0.00484

GnomAD3 exomes

AF:

0.00576

AC:

601

AN:

104360

Hom.:

AF XY:

0.00560

AC XY:

325

AN XY:

58066

show subpopulations

Gnomad AFR exome

AF:

0.00335

Gnomad AMR exome

AF:

0.00442

Gnomad ASJ exome

AF:

0.00704

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00204

Gnomad FIN exome

AF:

0.00243

Gnomad NFE exome

AF:

0.00945

Gnomad OTH exome

AF:

0.00506

GnomAD4 exome

AF:

0.00671

AC:

1766

AN:

263154

Hom.:

Cov.:

AF XY:

0.00630

AC XY:

958

AN XY:

152040

show subpopulations

Gnomad4 AFR exome

AF:

0.00342

Gnomad4 AMR exome

AF:

0.00405

Gnomad4 ASJ exome

AF:

0.00837

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00231

Gnomad4 FIN exome

AF:

0.00142

Gnomad4 NFE exome

AF:

0.00952

Gnomad4 OTH exome

AF:

0.00556

GnomAD4 genome

AF:

0.00667

AC:

1005

AN:

150762

Hom.:

Cov.:

AF XY:

0.00646

AC XY:

475

AN XY:

73530

show subpopulations

Gnomad4 AFR

AF:

0.00448

Gnomad4 AMR

AF:

0.00543

Gnomad4 ASJ

AF:

0.00722

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00231

Gnomad4 FIN

AF:

0.00222

Gnomad4 NFE

AF:

0.00990

Gnomad4 OTH

AF:

0.00479

Alfa

AF:

0.00852

Hom.:

Bravo

AF:

0.00656

TwinsUK

AF:

0.00863

AC:

ALSPAC

AF:

0.00882

AC:

ExAC

AF:

0.00285

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

EFCAB2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.38

CADD

Benign

0.057

DANN

Benign

0.69

DEOGEN2

Benign

0.0051

T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0025

LIST_S2

Benign

0.35

T;T

MetaRNN

Benign

0.0066

T;T

MetaSVM

Benign

-0.96

PROVEAN

Benign

-0.67

N;N

REVEL

Benign

0.18

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.0070

D;T

Polyphen

0.0010

B;.

Vest4

0.017

MVP

0.41

ClinPred

0.011

GERP RS

-0.32

Varity_R

0.074

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