13-106493156-C-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004093.4(EFNB2):​c.886G>T​(p.Ala296Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000144 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

EFNB2
NM_004093.4 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.90
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.18168685).
BS2
High AC in GnomAdExome4 at 21 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EFNB2NM_004093.4 linkuse as main transcriptc.886G>T p.Ala296Ser missense_variant 5/5 ENST00000646441.1
EFNB2NM_001372056.1 linkuse as main transcriptc.793G>T p.Ala265Ser missense_variant 4/4
EFNB2NM_001372057.1 linkuse as main transcriptc.772G>T p.Ala258Ser missense_variant 4/4
EFNB2XM_017020406.3 linkuse as main transcriptc.892G>T p.Ala298Ser missense_variant 5/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EFNB2ENST00000646441.1 linkuse as main transcriptc.886G>T p.Ala296Ser missense_variant 5/5 NM_004093.4 P1
ENST00000646480.1 linkuse as main transcriptn.496+278C>A intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000438
AC:
11
AN:
251422
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135892
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000703
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000144
AC:
21
AN:
1461824
Hom.:
0
Cov.:
30
AF XY:
0.0000124
AC XY:
9
AN XY:
727212
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.000182
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000658
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000119

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 06, 2021The c.886G>T (p.A296S) alteration is located in exon 5 (coding exon 5) of the EFNB2 gene. This alteration results from a G to T substitution at nucleotide position 886, causing the alanine (A) at amino acid position 296 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.072
BayesDel_addAF
Benign
-0.016
T
BayesDel_noAF
Uncertain
-0.070
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Benign
0.070
T;T
Eigen
Benign
-0.14
Eigen_PC
Benign
0.12
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.82
.;T
M_CAP
Benign
0.046
D
MetaRNN
Benign
0.18
T;T
MetaSVM
Benign
-0.37
T
MutationAssessor
Benign
-0.90
N;N
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.86
D
PROVEAN
Benign
-0.30
N;.
REVEL
Uncertain
0.36
Sift
Benign
0.53
T;.
Sift4G
Benign
1.0
T;.
Polyphen
0.044
B;B
Vest4
0.46
MVP
0.75
MPC
0.70
ClinPred
0.087
T
GERP RS
5.8
Varity_R
0.069
gMVP
0.43

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.

Other links and lift over

dbSNP: rs767538286; hg19: chr13-107145504; API