13-106521008-G-A

Position:

• chr13-106521008-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.123-8196C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 152,110 control chromosomes in the GnomAD database, including 50,245 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 0.81 (50245 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: EFNB2 NM_004093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.744

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]

ENSG00000284966 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFNB2	NM_004093.4	c.123-8196C>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.123-8196C>T		intron_variant			NM_004093.4	ENSP00000493716.1
ENSG00000284966	ENST00000646480.1	n.5372G>A		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes AF: 0.812 AC: 123364 AN: 151992 Hom.: 50213 Cov.: 31

Gnomad AFR AF: 0.752

Gnomad AMI AF: 0.894

Gnomad AMR AF: 0.800

Gnomad ASJ AF: 0.814

Gnomad EAS AF: 0.877

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.850

Gnomad MID AF: 0.777

Gnomad NFE AF: 0.839

Gnomad OTH AF: 0.812

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.812 AC: 123454 AN: 152110 Hom.: 50245 Cov.: 31 AF XY: 0.813 AC XY: 60457 AN XY: 74344

Gnomad4 AFR AF: 0.752

Gnomad4 AMR AF: 0.800

Gnomad4 ASJ AF: 0.814

Gnomad4 EAS AF: 0.877

Gnomad4 SAS AF: 0.808

Gnomad4 FIN AF: 0.850

Gnomad4 NFE AF: 0.839

Gnomad4 OTH AF: 0.810

Alfa AF: 0.836 Hom.: 51475

Bravo AF: 0.806

Asia WGS AF: 0.829 AC: 2886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	12
DANN	Benign	0.66

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: rs2391337; hg19: chr13-107173356;