chr13-106500621-C-G

Variant names:

• chr13-106500621-C-G
• rs9301140
• NM_004093.4:c.407-4781G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004093.4(EFNB2):​c.407-4781G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 152,142 control chromosomes in the GnomAD database, including 48,397 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 0.78 (48397 hom., cov: 32)
• Consequence: EFNB2 NM_004093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.748
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFNB2	NM_004093.4	c.407-4781G>C		intron_variant	Intron 2 of 4	ENST00000646441.1	NP_004084.1
EFNB2	NM_001372056.1	c.407-5627G>C		intron_variant	Intron 2 of 3		NP_001358985.1
EFNB2	NM_001372057.1	c.407-4781G>C		intron_variant	Intron 2 of 3		NP_001358986.1
EFNB2	XM_017020406.3	c.413-4781G>C		intron_variant	Intron 2 of 4		XP_016875895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFNB2	ENST00000646441.1	c.407-4781G>C		intron_variant	Intron 2 of 4		NM_004093.4	ENSP00000493716.1
ENSG00000284966	ENST00000642447.1	n.85+7743C>G		intron_variant	Intron 1 of 1
EFNB2	ENST00000643990.1	n.11-4781G>C		intron_variant	Intron 1 of 3
ENSG00000284966	ENST00000646480.1	n.496+7743C>G		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119167 AN: 152022 Hom.: 48384 Cov.: 32

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.958

Gnomad AMR AF: 0.872

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.890

Gnomad FIN AF: 0.866

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.866

Gnomad OTH AF: 0.810

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

GnomAD4 genome AF: 0.784 AC: 119210 AN: 152142 Hom.: 48397 Cov.: 32 AF XY: 0.790 AC XY: 58786 AN XY: 74386

African (AFR) AF: 0.547 AC: 22680 AN: 41430

American (AMR) AF: 0.872 AC: 13340 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.826 AC: 2866 AN: 3470

East Asian (EAS) AF: 0.995 AC: 5152 AN: 5180

South Asian (SAS) AF: 0.890 AC: 4291 AN: 4822

European-Finnish (FIN) AF: 0.866 AC: 9189 AN: 10610

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.866 AC: 58868 AN: 68012

Other (OTH) AF: 0.811 AC: 1714 AN: 2114

Alfa AF: 0.817 Hom.: 6462

Bravo AF: 0.774

Asia WGS AF: 0.908 AC: 3155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.093
DANN	Benign	0.39
PhyloP100		-0.75
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9301140; hg19: chr13-107152969;