Genetic Variant EFNB2:c.123-6584T>C (chr13-106519396-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.123-6584T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 151,944 control chromosomes in the GnomAD database, including 20,135 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 0.51 ( 20135 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

EFNB2
NM_004093.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0780

Publications

1 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=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFNB2	NM_004093.4 link	c.123-6584T>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.123-6584T>C		intron_variant	Intron 1 of 4		NM_004093.4	ENSP00000493716.1		P52799
ENSG00000284966	ENST00000646480.1 link	n.3760A>G		non_coding_transcript_exon_variant	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.507

AC:

76910

AN:

151826

Hom.:

20134

Cov.:

show subpopulations

Gnomad AFR

AF:

0.405

Gnomad AMI

AF:

0.645

Gnomad AMR

AF:

0.412

Gnomad ASJ

AF:

0.448

Gnomad EAS

AF:

0.456

Gnomad SAS

AF:

0.498

Gnomad FIN

AF:

0.622

Gnomad MID

AF:

0.385

Gnomad NFE

AF:

0.579

Gnomad OTH

AF:

0.480

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:

0.506

AC:

76944

AN:

151944

Hom.:

20135

Cov.:

AF XY:

0.506

AC XY:

37602

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.405

AC:

16759

AN:

41426

American (AMR)

AF:

0.412

AC:

6285

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.448

AC:

1553

AN:

3466

East Asian (EAS)

AF:

0.455

AC:

2352

AN:

5166

South Asian (SAS)

AF:

0.499

AC:

2398

AN:

4806

European-Finnish (FIN)

AF:

0.622

AC:

6556

AN:

10546

Middle Eastern (MID)

AF:

0.394

AC:

115

AN:

292

European-Non Finnish (NFE)

AF:

0.579

AC:

39335

AN:

67958

Other (OTH)

AF:

0.477

AC:

1004

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1920

3840

5759

7679

9599

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

692

1384

2076

2768

3460

<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:

0.551

Hom.:

64688

Bravo

AF:

0.482

Asia WGS

AF:

0.457

AC:

1587

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.43

(source)

DANN

Benign

0.57

PhyloP100

-0.078

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