Genetic Variant NM_004093.4:c.123-3489G>C (chr13-106516301-C-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.123-3489G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 152,096 control chromosomes in the GnomAD database, including 43,900 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 0.76 ( 43899 hom., cov: 31)

Exomes 𝑓: 0.67 ( 1 hom. )

Consequence

EFNB2
NM_004093.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.68

Publications

3 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:

Genome browser will be placed here

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=-0.92).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004093.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EFNB2	NM_004093.4	MANE Select	c.123-3489G>C	intron	N/A	NP_004084.1	P52799
EFNB2	NM_001372056.1		c.123-3489G>C	intron	N/A	NP_001358985.1
EFNB2	NM_001372057.1		c.123-3489G>C	intron	N/A	NP_001358986.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EFNB2	ENST00000646441.1	MANE Select	c.123-3489G>C	intron	N/A	ENSP00000493716.1	P52799
EFNB2	ENST00000955444.1		c.123-3489G>C	intron	N/A	ENSP00000625503.1
ENSG00000284966	ENST00000646480.1		n.665C>G	non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.759

AC:

115401

AN:

151972

Hom.:

43869

Cov.:

show subpopulations

Gnomad AFR

AF:

0.738

Gnomad AMI

AF:

0.871

Gnomad AMR

AF:

0.748

Gnomad ASJ

AF:

0.747

Gnomad EAS

AF:

0.747

Gnomad SAS

AF:

0.780

Gnomad FIN

AF:

0.773

Gnomad MID

AF:

0.712

Gnomad NFE

AF:

0.771

Gnomad OTH

AF:

0.771

GnomAD4 exome

AF:

0.667

AC:

AN:

Hom.:

Cov.:

AF XY:

0.750

AC XY:

AN XY:

show subpopulations

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)

AF:

0.750

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.759

AC:

115485

AN:

152090

Hom.:

43899

Cov.:

AF XY:

0.761

AC XY:

56549

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.738

AC:

30613

AN:

41492

American (AMR)

AF:

0.748

AC:

11444

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.747

AC:

2592

AN:

3470

East Asian (EAS)

AF:

0.747

AC:

3839

AN:

5140

South Asian (SAS)

AF:

0.781

AC:

3763

AN:

4820

European-Finnish (FIN)

AF:

0.773

AC:

8183

AN:

10584

Middle Eastern (MID)

AF:

0.731

AC:

215

AN:

294

European-Non Finnish (NFE)

AF:

0.771

AC:

52417

AN:

67978

Other (OTH)

AF:

0.771

AC:

1625

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1448

2896

4343

5791

7239

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

862

1724

2586

3448

4310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.705

Hom.:

2120

Bravo

AF:

0.756

Asia WGS

AF:

0.758

AC:

2637

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.021

(source)

DANN

Benign

0.51

PhyloP100

-3.7

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over