Genetic Variant NM_001406.4:c.*871G>A (chr17-7710447-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001406.4(EFNB3):c.*871G>A variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.447 in 152,598 control chromosomes in the GnomAD database, including 17,526 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 0.45 ( 17438 hom., cov: 33)

Exomes 𝑓: 0.61 ( 88 hom. )

Consequence

EFNB3
NM_001406.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.46

Publications

10 publications found

Variant links:

Genes affected

EFNB3 (HGNC:3228): (ephrin B3) EFNB3, a member of the ephrin gene family, is important in brain development as well as in its maintenance. Moreover, since levels of EFNB3 expression were particularly high in several forebrain subregions compared to other brain subregions, it may play a pivotal role in forebrain function. The EPH and EPH-related receptors comprise the largest subfamily of receptor protein-tyrosine kinases and have been implicated in mediating developmental events, particularly in the nervous system. EPH Receptors typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin ligands and receptors have been named by the Eph Nomenclature Committee (1997). 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. The Eph family of receptors are similarly divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. [provided by RefSeq, Jul 2008]

EFNB3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFNB3	NM_001406.4 link	c.*871G>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000226091.3	NP_001397.1	Q15768

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFNB3	ENST00000226091.3 link	c.*871G>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_001406.4	ENSP00000226091.2		Q15768

Frequencies

GnomAD3 genomes

AF:

0.447

AC:

67917

AN:

151984

Hom.:

17448

Cov.:

show subpopulations

Gnomad AFR

AF:

0.194

Gnomad AMI

AF:

0.566

Gnomad AMR

AF:

0.428

Gnomad ASJ

AF:

0.523

Gnomad EAS

AF:

0.389

Gnomad SAS

AF:

0.363

Gnomad FIN

AF:

0.591

Gnomad MID

AF:

0.528

Gnomad NFE

AF:

0.586

Gnomad OTH

AF:

0.469

GnomAD4 exome

AF:

0.606

AC:

302

AN:

498

Hom.:

Cov.:

AF XY:

0.577

AC XY:

179

AN XY:

310

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.750

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.250

AC:

AN:

European-Finnish (FIN)

AF:

0.616

AC:

260

AN:

422

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.558

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.446

AC:

67907

AN:

152100

Hom.:

17438

Cov.:

AF XY:

0.445

AC XY:

33057

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.194

AC:

8050

AN:

41476

American (AMR)

AF:

0.427

AC:

6527

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.523

AC:

1817

AN:

3472

East Asian (EAS)

AF:

0.388

AC:

2009

AN:

5172

South Asian (SAS)

AF:

0.362

AC:

1747

AN:

4822

European-Finnish (FIN)

AF:

0.591

AC:

6248

AN:

10566

Middle Eastern (MID)

AF:

0.537

AC:

158

AN:

294

European-Non Finnish (NFE)

AF:

0.586

AC:

39852

AN:

67992

Other (OTH)

AF:

0.465

AC:

983

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1768

3535

5303

7070

8838

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

604

1208

1812

2416

3020

<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:

0.531

Hom.:

35040

Bravo

AF:

0.424

Asia WGS

AF:

0.326

AC:

1135

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.93

PhyloP100

4.5

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