Genetic Variant EFNB2:c.123-8305C>T (chr13-106521117-G-A) – 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.123-8305C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 150,946 control chromosomes in the GnomAD database, including 16,526 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 0.44 ( 16526 hom., cov: 29)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

EFNB2
NM_004093.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.55

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:

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=-0.71).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.645 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.123-8305C>T	intron	N/A	NP_004084.1	P52799
EFNB2	NM_001372056.1		c.123-8305C>T	intron	N/A	NP_001358985.1
EFNB2	NM_001372057.1		c.123-8305C>T	intron	N/A	NP_001358986.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EFNB2	ENST00000646441.1	MANE Select	c.123-8305C>T	intron	N/A	ENSP00000493716.1	P52799
EFNB2	ENST00000955444.1		c.123-8305C>T	intron	N/A	ENSP00000625503.1
ENSG00000284966	ENST00000646480.1		n.5481G>A	non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.443

AC:

66855

AN:

150826

Hom.:

16472

Cov.:

show subpopulations

Gnomad AFR

AF:

0.651

Gnomad AMI

AF:

0.309

Gnomad AMR

AF:

0.525

Gnomad ASJ

AF:

0.386

Gnomad EAS

AF:

0.538

Gnomad SAS

AF:

0.465

Gnomad FIN

AF:

0.327

Gnomad MID

AF:

0.406

Gnomad NFE

AF:

0.313

Gnomad OTH

AF:

0.422

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: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.444

AC:

66967

AN:

150944

Hom.:

16526

Cov.:

AF XY:

0.445

AC XY:

32751

AN XY:

73584

show subpopulations

African (AFR)

AF:

0.652

AC:

26895

AN:

41252

American (AMR)

AF:

0.525

AC:

7926

AN:

15102

Ashkenazi Jewish (ASJ)

AF:

0.386

AC:

1336

AN:

3462

East Asian (EAS)

AF:

0.537

AC:

2725

AN:

5070

South Asian (SAS)

AF:

0.465

AC:

2220

AN:

4778

European-Finnish (FIN)

AF:

0.327

AC:

3352

AN:

10256

Middle Eastern (MID)

AF:

0.399

AC:

114

AN:

286

European-Non Finnish (NFE)

AF:

0.313

AC:

21230

AN:

67742

Other (OTH)

AF:

0.425

AC:

888

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1735

3471

5206

6942

8677

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

598

1196

1794

2392

2990

<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:

0.380

Hom.:

4432

Bravo

AF:

0.470

Asia WGS

AF:

0.530

AC:

1838

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.69

PhyloP100

1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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