rs4399422

Positions:

• chr13-106494162-G-A
• chr13-106494162-G-C

Variant summary

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

The NM_004093.4(EFNB2):​c.613+719C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 152,020 control chromosomes in the GnomAD database, including 15,320 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 0.44 (15320 hom., cov: 33)
• Consequence: EFNB2 NM_004093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.69

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=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFNB2	NM_004093.4	c.613+719C>T		intron_variant		ENST00000646441.1	NP_004084.1
EFNB2	NM_001372056.1	c.520+719C>T		intron_variant			NP_001358985.1
EFNB2	NM_001372057.1	c.500-734C>T		intron_variant			NP_001358986.1
EFNB2	XM_017020406.3	c.619+719C>T		intron_variant			XP_016875895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFNB2	ENST00000646441.1	c.613+719C>T		intron_variant			NM_004093.4	ENSP00000493716	P1
	ENST00000646480.1	n.496+1284G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67269 AN: 151900 Hom.: 15282 Cov.: 33

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.462

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

GnomAD4 genome AF: 0.443 AC: 67359 AN: 152020 Hom.: 15320 Cov.: 33 AF XY: 0.442 AC XY: 32805 AN XY: 74292

Gnomad4 AFR AF: 0.530

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.504

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.460

Alfa AF: 0.424 Hom.: 13596

Bravo AF: 0.457

Asia WGS AF: 0.461 AC: 1604 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	13
DANN	Benign	0.67

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: rs4399422; hg19: chr13-107146510;