chr13-106500922-A-T

Variant names:

• chr13-106500922-A-T
• rs9514540
• NM_004093.4:c.407-5082T>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_004093.4(EFNB2):​c.407-5082T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.826 in 152,140 control chromosomes in the GnomAD database, including 52,631 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 0.83 (52631 hom., cov: 32)
• Consequence: EFNB2 NM_004093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 1 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 -8 ACMG points.

• 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.407-5082T>A		intron_variant	Intron 2 of 4	ENST00000646441.1	NP_004084.1
EFNB2	NM_001372056.1	c.407-5928T>A		intron_variant	Intron 2 of 3		NP_001358985.1
EFNB2	NM_001372057.1	c.407-5082T>A		intron_variant	Intron 2 of 3		NP_001358986.1
EFNB2	XM_017020406.3	c.413-5082T>A		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.407-5082T>A		intron_variant	Intron 2 of 4		NM_004093.4	ENSP00000493716.1
ENSG00000284966	ENST00000642447.1	n.85+8044A>T		intron_variant	Intron 1 of 1
EFNB2	ENST00000643990.1	n.11-5082T>A		intron_variant	Intron 1 of 3
ENSG00000284966	ENST00000646480.1	n.496+8044A>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.826 AC: 125523 AN: 152022 Hom.: 52592 Cov.: 32

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.958

Gnomad AMR AF: 0.895

Gnomad ASJ AF: 0.828

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.906

Gnomad FIN AF: 0.876

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.876

Gnomad OTH AF: 0.841

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

GnomAD4 genome AF: 0.826 AC: 125612 AN: 152140 Hom.: 52631 Cov.: 32 AF XY: 0.831 AC XY: 61822 AN XY: 74382

African (AFR) AF: 0.670 AC: 27773 AN: 41450

American (AMR) AF: 0.895 AC: 13683 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.828 AC: 2874 AN: 3472

East Asian (EAS) AF: 0.995 AC: 5156 AN: 5184

South Asian (SAS) AF: 0.906 AC: 4370 AN: 4824

European-Finnish (FIN) AF: 0.876 AC: 9274 AN: 10590

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.876 AC: 59591 AN: 68016

Other (OTH) AF: 0.841 AC: 1777 AN: 2112

Alfa AF: 0.848 Hom.: 6470

Bravo AF: 0.820

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	19
DANN	Benign	0.36
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.37		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.22		Position offset: 44
DS_DG_spliceai		0.37		Position offset: 3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9514540; hg19: chr13-107153270;