Genetic Variant EFNB2:p.Ser260Ser (chr13-106493262-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_004093.4(EFNB2):c.780G>A(p.Ser260Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0216 in 1,614,152 control chromosomes in the GnomAD database, including 429 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.017 ( 28 hom., cov: 33)

Exomes 𝑓: 0.022 ( 401 hom. )

Consequence

EFNB2
NM_004093.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.21

Variant links:

Genes affected

EFNB2 (HGNC:3227): (ephrin B2) This gene encodes a member of the ephrin (EPH) family. The ephrins and EPH-related receptors comprise the largest subfamily of receptor protein-tyrosine kinases and have been implicated in mediating developmental events, especially in the nervous system and in erythropoiesis. Based on their structures and sequence relationships, ephrins are divided into the ephrin-A (EFNA) class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B (EFNB) class, which are transmembrane proteins. This gene encodes an EFNB class ephrin which binds to the EPHB4 and EPHA3 receptors. [provided by RefSeq, Jul 2008]

EFNB2 links:

ENSG00000284966 (HGNC:):

ENSG00000284966 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 13-106493262-C-T is Benign according to our data. Variant chr13-106493262-C-T is described in ClinVar as [Benign]. Clinvar id is 3352657.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0166 (2521/152262) while in subpopulation NFE AF= 0.026 (1768/68016). AF 95% confidence interval is 0.025. There are 28 homozygotes in gnomad4. There are 1159 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2521 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFNB2	NM_004093.4 link	c.780G>A	p.Ser260Ser	synonymous_variant	Exon 5 of 5	ENST00000646441.1	NP_004084.1	P52799
EFNB2	NM_001372056.1 link	c.687G>A	p.Ser229Ser	synonymous_variant	Exon 4 of 4		NP_001358985.1
EFNB2	NM_001372057.1 link	c.666G>A	p.Ser222Ser	synonymous_variant	Exon 4 of 4		NP_001358986.1
EFNB2	XM_017020406.3 link	c.786G>A	p.Ser262Ser	synonymous_variant	Exon 5 of 5		XP_016875895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFNB2	ENST00000646441.1 link	c.780G>A	p.Ser260Ser	synonymous_variant	Exon 5 of 5		NM_004093.4	ENSP00000493716.1		P52799

Frequencies

GnomAD3 genomes

AF:

0.0166

AC:

2522

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00466

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0124

Gnomad ASJ

AF:

0.0236

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00559

Gnomad FIN

AF:

0.0203

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0260

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.0169

AC:

4247

AN:

251464

Hom.:

AF XY:

0.0170

AC XY:

2306

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.00498

Gnomad AMR exome

AF:

0.00931

Gnomad ASJ exome

AF:

0.0237

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00487

Gnomad FIN exome

AF:

0.0178

Gnomad NFE exome

AF:

0.0260

Gnomad OTH exome

AF:

0.0181

GnomAD4 exome

AF:

0.0222

AC:

32397

AN:

1461890

Hom.:

401

Cov.:

AF XY:

0.0219

AC XY:

15902

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00326

Gnomad4 AMR exome

AF:

0.0105

Gnomad4 ASJ exome

AF:

0.0224

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00544

Gnomad4 FIN exome

AF:

0.0195

Gnomad4 NFE exome

AF:

0.0255

Gnomad4 OTH exome

AF:

0.0205

GnomAD4 genome

AF:

0.0166

AC:

2521

AN:

152262

Hom.:

Cov.:

AF XY:

0.0156

AC XY:

1159

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00464

Gnomad4 AMR

AF:

0.0123

Gnomad4 ASJ

AF:

0.0236

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00560

Gnomad4 FIN

AF:

0.0203

Gnomad4 NFE

AF:

0.0260

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.0231

Hom.:

Bravo

AF:

0.0162

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0247

EpiControl

AF:

0.0248

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

EFNB2-related disorder

Benign:1

Sep 21, 2024

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

5.9

DANN

Benign

0.79

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