rs4772795

Positions:

• chr13-106517046-G-A

Variant summary

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

The NM_004093.4(EFNB2):​c.123-4234C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 152,048 control chromosomes in the GnomAD database, including 41,985 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 0.74 (41985 hom., cov: 32)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: EFNB2 NM_004093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930

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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFNB2	NM_004093.4	c.123-4234C>T		intron_variant		ENST00000646441.1	NP_004084.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFNB2	ENST00000646441.1	c.123-4234C>T		intron_variant			NM_004093.4	ENSP00000493716	P1
	ENST00000646480.1	n.1410G>A		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112687 AN: 151924 Hom.: 41954 Cov.: 32

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.871

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.746

Gnomad EAS AF: 0.732

Gnomad SAS AF: 0.779

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.761

GnomAD4 exome AF: 0.167 AC: 1 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

Gnomad4 AFR exome AF: 0.00

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.742 AC: 112770 AN: 152042 Hom.: 41985 Cov.: 32 AF XY: 0.744 AC XY: 55292 AN XY: 74316

Gnomad4 AFR AF: 0.683

Gnomad4 AMR AF: 0.740

Gnomad4 ASJ AF: 0.746

Gnomad4 EAS AF: 0.731

Gnomad4 SAS AF: 0.779

Gnomad4 FIN AF: 0.774

Gnomad4 NFE AF: 0.769

Gnomad4 OTH AF: 0.760

Alfa AF: 0.765 Hom.: 61337

Bravo AF: 0.734

Asia WGS AF: 0.748 AC: 2604 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.79
DANN	Benign	0.40

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: rs4772795; hg19: chr13-107169394;