Genetic Variant EFNB2:c.123-6825A>C (chr13-106519637-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004093.4(EFNB2):c.123-6825A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 152,002 control chromosomes in the GnomAD database, including 20,495 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.50 ( 20495 hom., cov: 33)

Failed GnomAD Quality Control

Consequence

EFNB2
NM_004093.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.208

Publications

4 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFNB2	NM_004093.4 link	c.123-6825A>C		intron_variant	Intron 1 of 4	ENST00000646441.1	NP_004084.1	P52799

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFNB2	ENST00000646441.1 link	c.123-6825A>C		intron_variant	Intron 1 of 4		NM_004093.4	ENSP00000493716.1		P52799
ENSG00000284966	ENST00000646480.1 link	n.4001T>G		non_coding_transcript_exon_variant	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.504

AC:

76608

AN:

151884

Hom.:

20497

Cov.:

show subpopulations

Gnomad AFR

AF:

0.317

Gnomad AMI

AF:

0.631

Gnomad AMR

AF:

0.540

Gnomad ASJ

AF:

0.454

Gnomad EAS

AF:

0.634

Gnomad SAS

AF:

0.536

Gnomad FIN

AF:

0.638

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.579

Gnomad OTH

AF:

0.495

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.504

AC:

76634

AN:

152002

Hom.:

20495

Cov.:

AF XY:

0.511

AC XY:

37952

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.317

AC:

13125

AN:

41456

American (AMR)

AF:

0.540

AC:

8255

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.454

AC:

1577

AN:

3470

East Asian (EAS)

AF:

0.634

AC:

3273

AN:

5164

South Asian (SAS)

AF:

0.536

AC:

2582

AN:

4814

European-Finnish (FIN)

AF:

0.638

AC:

6736

AN:

10550

Middle Eastern (MID)

AF:

0.408

AC:

120

AN:

294

European-Non Finnish (NFE)

AF:

0.579

AC:

39355

AN:

67960

Other (OTH)

AF:

0.492

AC:

1038

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1868

3735

5603

7470

9338

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.543

Hom.:

34626

Bravo

AF:

0.487

Asia WGS

AF:

0.541

AC:

1879

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.3

(source)

DANN

Benign

0.68

PhyloP100

0.21

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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13-106519637-T-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over