rs3742160

chr13-106493481-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004093.4(EFNB2):c.614-53T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 1,548,130 control chromosomes in the GnomAD database, including 65,184 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 0.31 (7696 hom., cov: 32)
  • Exomes 𝑓: 0.28 (57488 hom.)
• Consequence: EFNB2 NM_004093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFNB2	NM_004093.4	c.614-53T>A		intron_variant		ENST00000646441.1
EFNB2	NM_001372056.1	c.521-53T>A		intron_variant
EFNB2	NM_001372057.1	c.500-53T>A		intron_variant
EFNB2	XM_017020406.3	c.620-53T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFNB2	ENST00000646441.1	c.614-53T>A		intron_variant			NM_004093.4	P1
	ENST00000646480.1	n.496+603A>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47351 AN: 151976 Hom.: 7673 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.339

GnomAD4 exome AF: 0.281 AC: 392486 AN: 1396036 Hom.: 57488 AF XY: 0.284 AC XY: 195096 AN XY: 686800

Gnomad4 AFR exome AF: 0.379

Gnomad4 AMR exome AF: 0.421

Gnomad4 ASJ exome AF: 0.327

Gnomad4 EAS exome AF: 0.441

Gnomad4 SAS exome AF: 0.394

Gnomad4 FIN exome AF: 0.220

Gnomad4 NFE exome AF: 0.260

Gnomad4 OTH exome AF: 0.303

GnomAD4 genome AF: 0.312 AC: 47414 AN: 152094 Hom.: 7696 Cov.: 32 AF XY: 0.313 AC XY: 23265 AN XY: 74356

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.424

Gnomad4 SAS AF: 0.408

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.337

Alfa AF: 0.282 Hom.: 799

Bravo AF: 0.327

Asia WGS AF: 0.395 AC: 1378 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	0.12
Dann	Benign	0.55

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: rs3742160; hg19: chr13-107145829; COSMIC: COSV55363908;