rs9520094

chr13-106530708-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.122+4135A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,126 control chromosomes in the GnomAD database, including 6,322 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 0.28 (6322 hom., cov: 32)
• Consequence: EFNB2 NM_004093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFNB2	NM_004093.4	c.122+4135A>C		intron_variant		ENST00000646441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFNB2	ENST00000646441.1	c.122+4135A>C		intron_variant			NM_004093.4	P1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43024 AN: 152008 Hom.: 6321 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.283 AC: 43041 AN: 152126 Hom.: 6322 Cov.: 32 AF XY: 0.283 AC XY: 21021 AN XY: 74376

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.136

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.303

Alfa AF: 0.302 Hom.: 7901

Bravo AF: 0.282

Asia WGS AF: 0.199 AC: 694 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	8.1
Dann	Benign	0.71

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: rs9520094; hg19: chr13-107183056;