Genetic Variant NM_004093.4:c.123-95G>C (chr13-106512907-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.123-95G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 1,064,862 control chromosomes in the GnomAD database, including 144,490 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 0.45 ( 17009 hom., cov: 32)

Exomes 𝑓: 0.52 ( 127481 hom. )

Consequence

EFNB2
NM_004093.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.541

Publications

6 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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFNB2	NM_004093.4 link	c.123-95G>C		intron_variant	Intron 1 of 4	ENST00000646441.1	NP_004084.1	P52799

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
EFNB2	ENST00000646441.1 link	c.123-95G>C	intron_variant	Intron 1 of 4	NM_004093.4	ENSP00000493716.1	P52799
EFNB2	ENST00000643990.1 link	n.10+3531G>C	intron_variant	Intron 1 of 3
ENSG00000284966	ENST00000646480.1 link	n.497-3226C>G	intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.454

AC:

68971

AN:

151826

Hom.:

17001

Cov.:

show subpopulations

Gnomad AFR

AF:

0.256

Gnomad AMI

AF:

0.612

Gnomad AMR

AF:

0.475

Gnomad ASJ

AF:

0.416

Gnomad EAS

AF:

0.578

Gnomad SAS

AF:

0.494

Gnomad FIN

AF:

0.597

Gnomad MID

AF:

0.380

Gnomad NFE

AF:

0.536

Gnomad OTH

AF:

0.451

GnomAD4 exome

AF:

0.524

AC:

478341

AN:

912918

Hom.:

127481

AF XY:

0.523

AC XY:

238849

AN XY:

456320

show subpopulations

African (AFR)

AF:

0.252

AC:

5528

AN:

21974

American (AMR)

AF:

0.447

AC:

10943

AN:

24462

Ashkenazi Jewish (ASJ)

AF:

0.410

AC:

6562

AN:

16004

East Asian (EAS)

AF:

0.571

AC:

20696

AN:

36226

South Asian (SAS)

AF:

0.499

AC:

21465

AN:

43052

European-Finnish (FIN)

AF:

0.595

AC:

21144

AN:

35564

Middle Eastern (MID)

AF:

0.420

AC:

1187

AN:

2828

European-Non Finnish (NFE)

AF:

0.535

AC:

370598

AN:

692386

Other (OTH)

AF:

0.500

AC:

20218

AN:

40422

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

11062

22124

33185

44247

55309

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9736

19472

29208

38944

48680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.454

AC:

68994

AN:

151944

Hom.:

17009

Cov.:

AF XY:

0.461

AC XY:

34229

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.255

AC:

10582

AN:

41442

American (AMR)

AF:

0.475

AC:

7248

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.416

AC:

1444

AN:

3468

East Asian (EAS)

AF:

0.577

AC:

2984

AN:

5170

South Asian (SAS)

AF:

0.496

AC:

2384

AN:

4810

European-Finnish (FIN)

AF:

0.597

AC:

6288

AN:

10528

Middle Eastern (MID)

AF:

0.391

AC:

115

AN:

294

European-Non Finnish (NFE)

AF:

0.536

AC:

36435

AN:

67942

Other (OTH)

AF:

0.454

AC:

957

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1788

3577

5365

7154

8942

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

636

1272

1908

2544

3180

<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:

0.493

Hom.:

2461

Bravo

AF:

0.434

Asia WGS

AF:

0.520

AC:

1805

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.2

(source)

DANN

Benign

0.41

PhyloP100

-0.54

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over