rs11069646

Positions:

• chr13-106504772-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.406+7757C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 151,854 control chromosomes in the GnomAD database, including 19,444 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 (19444 hom., cov: 31)
• Consequence: EFNB2 NM_004093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFNB2	NM_004093.4	c.406+7757C>T		intron_variant		ENST00000646441.1
EFNB2	NM_001372056.1	c.406+7757C>T		intron_variant
EFNB2	NM_001372057.1	c.406+7757C>T		intron_variant
EFNB2	XM_017020406.3	c.412+7757C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFNB2	ENST00000646441.1	c.406+7757C>T		intron_variant			NM_004093.4	P1
	ENST00000646480.1	n.497-11361G>A		intron_variant, non_coding_transcript_variant
	ENST00000642447.1	n.86-5047G>A		intron_variant, non_coding_transcript_variant
EFNB2	ENST00000643990.1	n.11-8932C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75281 AN: 151736 Hom.: 19433 Cov.: 31

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.486

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

GnomAD4 genome AF: 0.496 AC: 75307 AN: 151854 Hom.: 19444 Cov.: 31 AF XY: 0.499 AC XY: 37042 AN XY: 74200

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.500

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.564

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.566

Gnomad4 OTH AF: 0.489

Alfa AF: 0.541 Hom.: 3821

Bravo AF: 0.479

Asia WGS AF: 0.521 AC: 1809 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	0.049
DANN	Benign	0.36

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: rs11069646; hg19: chr13-107157120;