rs7490924

Variant names:

• chr13-106519396-A-G
• rs7490924
• NM_004093.4:c.123-6584T>C

Variant summary

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

The NM_004093.4(EFNB2):​c.123-6584T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 151,944 control chromosomes in the GnomAD database, including 20,135 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 0.51 (20135 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: EFNB2 NM_004093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFNB2	NM_004093.4	c.123-6584T>C		intron_variant	Intron 1 of 4	ENST00000646441.1	NP_004084.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFNB2	ENST00000646441.1	c.123-6584T>C		intron_variant	Intron 1 of 4		NM_004093.4	ENSP00000493716.1
ENSG00000284966	ENST00000646480.1	n.3760A>G		non_coding_transcript_exon_variant	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76910 AN: 151826 Hom.: 20134 Cov.: 32

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.480

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: 0.506 AC: 76944 AN: 151944 Hom.: 20135 Cov.: 32 AF XY: 0.506 AC XY: 37602 AN XY: 74242

Gnomad4 AFR AF: 0.405

Gnomad4 AMR AF: 0.412

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.455

Gnomad4 SAS AF: 0.499

Gnomad4 FIN AF: 0.622

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.477

Alfa AF: 0.555 Hom.: 29163

Bravo AF: 0.482

Asia WGS AF: 0.457 AC: 1587 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	0.43
DANN	Benign	0.57

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: rs7490924; hg19: chr13-107171744;