Variant 17-62373824-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001144933.2(EFCAB3):c.45G>C(p.Lys15Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00351 in 1,511,846 control chromosomes in the GnomAD database, including 171 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 95 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 76 hom. )

Consequence

EFCAB3
NM_001144933.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.490

Variant links:

Genes affected

EFCAB3 (HGNC:26379): (EF-hand calcium binding domain 3) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

EFCAB3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022574067).

BP6

Variant 17-62373824-G-C is Benign according to our data. Variant chr17-62373824-G-C is described in ClinVar as [Benign]. Clinvar id is 770272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.065 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFCAB3	NM_001144933.2 linkuse as main transcript	c.45G>C	p.Lys15Asn	missense_variant	2/12		NP_001138405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFCAB3	ENST00000450662.7 linkuse as main transcript	c.45G>C	p.Lys15Asn	missense_variant	2/12	5		ENSP00000403932		Q8N7B9-2
EFCAB3	ENST00000636041.1 linkuse as main transcript	n.274G>C		non_coding_transcript_exon_variant	4/14	5

Frequencies

GnomAD3 genomes

AF:

0.0193

AC:

2939

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0673

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00694

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.00434

AC:

652

AN:

150200

Hom.:

AF XY:

0.00321

AC XY:

255

AN XY:

79558

show subpopulations

Gnomad AFR exome

AF:

0.0708

Gnomad AMR exome

AF:

0.00277

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:

0.000374

Gnomad OTH exome

AF:

0.00257

GnomAD4 exome

AF:

0.00174

AC:

2369

AN:

1359624

Hom.:

Cov.:

AF XY:

0.00146

AC XY:

979

AN XY:

672232

show subpopulations

Gnomad4 AFR exome

AF:

0.0625

Gnomad4 AMR exome

AF:

0.00337

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000390

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000125

Gnomad4 OTH exome

AF:

0.00384

GnomAD4 genome

AF:

0.0193

AC:

2937

AN:

152222

Hom.:

Cov.:

AF XY:

0.0190

AC XY:

1412

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0671

Gnomad4 AMR

AF:

0.00693

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.00276

Hom.:

Bravo

AF:

0.0215

ExAC

AF:

0.00737

AC:

156

Asia WGS

AF:

0.00231

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.96

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.42

MetaRNN

Benign

0.0023

MetaSVM

Benign

-0.95

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.66

REVEL

Benign

0.040

Sift

Pathogenic

0.0

Sift4G

Benign

0.14

Vest4

0.22

MutPred

0.37

Loss of ubiquitination at K15 (P = 0.0155);

MVP

0.13

MPC

0.36

ClinPred

0.056

GERP RS

0.79

gMVP

0.19

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