rs10508175

chr13-106515500-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_004093.4(EFNB2):c.123-2688A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 152,294 control chromosomes in the GnomAD database, including 13 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 0.012 (13 hom., cov: 32)
• Consequence: EFNB2 NM_004093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.178

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS2: High AC in GnomAd at 1894 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFNB2	NM_004093.4	c.123-2688A>G		intron_variant		ENST00000646441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFNB2	ENST00000646441.1	c.123-2688A>G		intron_variant			NM_004093.4	P1
	ENST00000646480.1	n.497-633T>C		intron_variant, non_coding_transcript_variant
EFNB2	ENST00000643990.1	n.10+938A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0124 AC: 1894 AN: 152176 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.0122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0124

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.0112

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0152

Gnomad OTH AF: 0.0139

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0124 AC: 1895 AN: 152294 Hom.: 13 Cov.: 32 AF XY: 0.0115 AC XY: 856 AN XY: 74478

Gnomad4 AFR AF: 0.0122

Gnomad4 AMR AF: 0.0124

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.0112

Gnomad4 NFE AF: 0.0152

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.0150 Hom.: 5

Bravo AF: 0.0130

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.9
Dann	Benign	0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs10508175; hg19: chr13-107167848;