Variant 17-62391965-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The ENST00000305286.8(EFCAB3):c.295C>T(p.Arg99Ter) variant causes a stop gained, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00735 in 1,592,754 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts 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 Likely benign (★★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0067 ( 11 hom., cov: 31)

Exomes 𝑓: 0.0074 ( 80 hom. )

Consequence

EFCAB3
ENST00000305286.8 stop_gained, splice_region

Scores

Splicing: ADA: 0.002096

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.656

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 -12 ACMG points.

BP6

Variant 17-62391965-C-T is Benign according to our data. Variant chr17-62391965-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 787599.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
EFCAB3	NM_173503.4 linkuse as main transcript	c.295C>T	p.Arg99Ter	stop_gained, splice_region_variant	4/10	ENST00000305286.8	NP_775774.1
EFCAB3	NM_001144933.2 linkuse as main transcript	c.451C>T	p.Arg151Ter	stop_gained, splice_region_variant	6/12		NP_001138405.1
EFCAB3	XM_011524381.3 linkuse as main transcript	c.361C>T	p.Arg121Ter	stop_gained, splice_region_variant	4/10		XP_011522683.2
EFCAB3	XM_011524380.2 linkuse as main transcript	c.295C>T	p.Arg99Ter	stop_gained, splice_region_variant	4/10		XP_011522682.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFCAB3	ENST00000305286.8 linkuse as main transcript	c.295C>T	p.Arg99Ter	stop_gained, splice_region_variant	4/10	1	NM_173503.4	ENSP00000302649	P1	Q8N7B9-1

Frequencies

GnomAD3 genomes

AF:

0.00666

AC:

1012

AN:

151850

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000895

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00315

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.0451

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00624

Gnomad OTH

AF:

0.00479

GnomAD3 exomes

AF:

0.00774

AC:

1911

AN:

247058

Hom.:

AF XY:

0.00770

AC XY:

1030

AN XY:

133700

show subpopulations

Gnomad AFR exome

AF:

0.00149

Gnomad AMR exome

AF:

0.00170

Gnomad ASJ exome

AF:

0.00171

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000940

Gnomad FIN exome

AF:

0.0448

Gnomad NFE exome

AF:

0.00702

Gnomad OTH exome

AF:

0.00502

GnomAD4 exome

AF:

0.00742

AC:

10697

AN:

1440792

Hom.:

Cov.:

AF XY:

0.00728

AC XY:

5216

AN XY:

716414

show subpopulations

Gnomad4 AFR exome

AF:

0.000903

Gnomad4 AMR exome

AF:

0.00188

Gnomad4 ASJ exome

AF:

0.00239

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00116

Gnomad4 FIN exome

AF:

0.0422

Gnomad4 NFE exome

AF:

0.00712

Gnomad4 OTH exome

AF:

0.00638

GnomAD4 genome

AF:

0.00666

AC:

1012

AN:

151962

Hom.:

Cov.:

AF XY:

0.00819

AC XY:

608

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.000892

Gnomad4 AMR

AF:

0.00315

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0451

Gnomad4 NFE

AF:

0.00624

Gnomad4 OTH

AF:

0.00474

Alfa

AF:

0.00601

Hom.:

Bravo

AF:

0.00389

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00500

AC:

ExAC

AF:

0.00690

AC:

838

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	EFCAB3: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

DANN

Benign

0.93

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.019

M_CAP

Benign

0.016

MutationTaster

Benign

1.0

A;A

Vest4

0.27

GERP RS

-7.6

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0021

dbscSNV1_RF

Benign

0.19

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

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