rs2391339

chr13-106521117-G-Achr13-106521117-G-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55

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=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFNB2	NM_004093.4	c.123-8305C>T		intron_variant		ENST00000646441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFNB2	ENST00000646441.1	c.123-8305C>T		intron_variant			NM_004093.4	P1
	ENST00000646480.1	n.5481G>A		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes AF: 0.443 AC: 66855 AN: 150826 Hom.: 16472 Cov.: 29

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: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.444 AC: 66967 AN: 150944 Hom.: 16526 Cov.: 29 AF XY: 0.445 AC XY: 32751 AN XY: 73584

Gnomad4 AFR AF: 0.652

Gnomad4 AMR AF: 0.525

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.465

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.425

Alfa AF: 0.363 Hom.: 2256

Bravo AF: 0.470

Asia WGS AF: 0.530 AC: 1838 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	13
Dann	Benign	0.69

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

LitVar

Other links and lift over

dbSNP: rs2391339; hg19: chr13-107173465;