13-106519637-T-G

Variant summary

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

The NM_004093.4(EFNB2):c.123-6825A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 152,002 control chromosomes in the GnomAD database, including 20,495 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 0.50 (20495 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: EFNB2 NM_004093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.208

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFNB2	NM_004093.4	c.123-6825A>C		intron_variant		ENST00000646441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFNB2	ENST00000646441.1	c.123-6825A>C		intron_variant			NM_004093.4	P1
	ENST00000646480.1	n.4001T>G		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76608 AN: 151884 Hom.: 20497 Cov.: 33

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.495

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: 0.504 AC: 76634 AN: 152002 Hom.: 20495 Cov.: 33 AF XY: 0.511 AC XY: 37952 AN XY: 74288

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.540

Gnomad4 ASJ AF: 0.454

Gnomad4 EAS AF: 0.634

Gnomad4 SAS AF: 0.536

Gnomad4 FIN AF: 0.638

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.492

Alfa AF: 0.551 Hom.: 28062

Bravo AF: 0.487

Asia WGS AF: 0.541 AC: 1879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	2.3
Dann	Benign	0.68

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: rs2391335; hg19: chr13-107171985;