rs3744262

chr17-7710447-G-Achr17-7710447-G-Cchr17-7710447-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.46

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
EFNB3	NM_001406.4	c.*871G>A		3_prime_UTR_variant	5/5	ENST00000226091.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFNB3	ENST00000226091.3	c.*871G>A		3_prime_UTR_variant	5/5	1	NM_001406.4	P1

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67917 AN: 151984 Hom.: 17448 Cov.: 33

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.: 88 Cov.: 0 AF XY: 0.577 AC XY: 179 AN XY: 310

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.750

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.616

Gnomad4 NFE exome AF: 0.558

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.446 AC: 67907 AN: 152100 Hom.: 17438 Cov.: 33 AF XY: 0.445 AC XY: 33057 AN XY: 74334

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.523

Gnomad4 EAS AF: 0.388

Gnomad4 SAS AF: 0.362

Gnomad4 FIN AF: 0.591

Gnomad4 NFE AF: 0.586

Gnomad4 OTH AF: 0.465

Alfa AF: 0.540 Hom.: 24330

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	19
Dann	Benign	0.93

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

LitVar

Other links and lift over

dbSNP: rs3744262; hg19: chr17-7613765; COSMIC: COSV56833530;