Variant rs147599832 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004429.5(EFNB1):c.509C>T(p.Ala170Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.001 in 1,210,488 control chromosomes in the GnomAD database, including 12 homozygotes. There are 339 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0053 ( 4 hom., 163 hem., cov: 24)

Exomes 𝑓: 0.00056 ( 8 hom. 176 hem. )

Consequence

EFNB1
NM_004429.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.26

Variant links:

Genes affected

EFNB1 (HGNC:3226): (ephrin B1) The protein encoded by this gene is a type I membrane protein and a ligand of Eph-related receptor tyrosine kinases. It may play a role in cell adhesion and function in the development or maintenance of the nervous system. [provided by RefSeq, Jul 2008]

EFNB1 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=0.0074879825).

BP6

Variant X-68839969-C-T is Benign according to our data. Variant chrX-68839969-C-T is described in ClinVar as [Benign]. Clinvar id is 376763.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-68839969-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00533 (600/112482) while in subpopulation AFR AF= 0.0184 (570/30983). AF 95% confidence interval is 0.0171. There are 4 homozygotes in gnomad4. There are 163 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFNB1	NM_004429.5 linkuse as main transcript	c.509C>T	p.Ala170Val	missense_variant	4/5	ENST00000204961.5	NP_004420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFNB1	ENST00000204961.5 linkuse as main transcript	c.509C>T	p.Ala170Val	missense_variant	4/5	1	NM_004429.5	ENSP00000204961	P1

Frequencies

GnomAD3 genomes

AF:

0.00535

AC:

601

AN:

112429

Hom.:

Cov.:

AF XY:

0.00471

AC XY:

163

AN XY:

34587

show subpopulations

Gnomad AFR

AF:

0.0185

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00233

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:

0.0000188

Gnomad OTH

AF:

0.00265

GnomAD3 exomes

AF:

0.00151

AC:

275

AN:

182215

Hom.:

AF XY:

0.00108

AC XY:

AN XY:

66807

show subpopulations

Gnomad AFR exome

AF:

0.0181

Gnomad AMR exome

AF:

0.00132

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:

0.00

Gnomad OTH exome

AF:

0.000443

GnomAD4 exome

AF:

0.000557

AC:

612

AN:

1098006

Hom.:

Cov.:

AF XY:

0.000484

AC XY:

176

AN XY:

363366

show subpopulations

Gnomad4 AFR exome

AF:

0.0189

Gnomad4 AMR exome

AF:

0.00142

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000831

Gnomad4 OTH exome

AF:

0.00115

GnomAD4 genome

AF:

0.00533

AC:

600

AN:

112482

Hom.:

Cov.:

AF XY:

0.00470

AC XY:

163

AN XY:

34650

show subpopulations

Gnomad4 AFR

AF:

0.0184

Gnomad4 AMR

AF:

0.00233

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00261

Alfa

AF:

0.000484

Hom.:

Bravo

AF:

0.00701

ESP6500AA

AF:

0.0146

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00188

AC:

228

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jan 09, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 19, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 25, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.22

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.85

MetaRNN

Benign

0.0075

MetaSVM

Uncertain

-0.13

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-2.2

REVEL

Uncertain

0.29

Sift

Benign

0.11

Sift4G

Benign

0.49

Polyphen

0.42

Vest4

0.29

MVP

0.87

MPC

0.70

ClinPred

0.025

GERP RS

5.1

Varity_R

0.22

gMVP

0.86

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

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