Genetic Variant NM_004093.4:c.406+5951T>C (chr13-106506578-A-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.406+5951T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 152,044 control chromosomes in the GnomAD database, including 31,228 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 0.64 ( 31228 hom., cov: 32)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

EFNB2
NM_004093.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0530

Publications

0 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:

ENSG00000274204 (HGNC:):

ENSG00000274204 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=-0.61).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFNB2	NM_004093.4 link	c.406+5951T>C		intron_variant	Intron 2 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.406+5951T>C		intron_variant	Intron 2 of 4		NM_004093.4	ENSP00000493716.1		P52799

Frequencies

GnomAD3 genomes

AF:

0.638

AC:

96874

AN:

151924

Hom.:

31224

Cov.:

show subpopulations

Gnomad AFR

AF:

0.556

Gnomad AMI

AF:

0.582

Gnomad AMR

AF:

0.598

Gnomad ASJ

AF:

0.614

Gnomad EAS

AF:

0.572

Gnomad SAS

AF:

0.588

Gnomad FIN

AF:

0.735

Gnomad MID

AF:

0.599

Gnomad NFE

AF:

0.692

Gnomad OTH

AF:

0.622

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

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:

0.500

AC:

AN:

Other (OTH)

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:

0.637

AC:

96902

AN:

152042

Hom.:

31228

Cov.:

AF XY:

0.638

AC XY:

47404

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.555

AC:

23009

AN:

41452

American (AMR)

AF:

0.598

AC:

9135

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.614

AC:

2129

AN:

3466

East Asian (EAS)

AF:

0.571

AC:

2945

AN:

5156

South Asian (SAS)

AF:

0.589

AC:

2836

AN:

4812

European-Finnish (FIN)

AF:

0.735

AC:

7777

AN:

10584

Middle Eastern (MID)

AF:

0.592

AC:

173

AN:

292

European-Non Finnish (NFE)

AF:

0.692

AC:

47046

AN:

67968

Other (OTH)

AF:

0.625

AC:

1321

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1808

3617

5425

7234

9042

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

786

1572

2358

3144

3930

<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:

0.650

Hom.:

12365

Bravo

AF:

0.620

Asia WGS

AF:

0.587

AC:

2040

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

3.8

(source)

DANN

Benign

0.81

PhyloP100

0.053

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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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