13-106506578-A-G

Variant names:

• chr13-106506578-A-G
• rs9587148
• NM_004093.4:c.406+5951T>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.406+5951T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 152,044 control chromosomes in the GnomAD database, including 31,228 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 0.64 (31228 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: EFNB2 NM_004093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530
• Publications: 0 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]

ENSG00000274204 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFNB2	NM_004093.4	c.406+5951T>C		intron_variant	Intron 2 of 4	ENST00000646441.1	NP_004084.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFNB2	ENST00000646441.1	c.406+5951T>C		intron_variant	Intron 2 of 4		NM_004093.4	ENSP00000493716.1

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96874 AN: 151924 Hom.: 31224 Cov.: 32

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.622

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.637 AC: 96902 AN: 152042 Hom.: 31228 Cov.: 32 AF XY: 0.638 AC XY: 47404 AN XY: 74348

African (AFR) AF: 0.555 AC: 23009 AN: 41452

American (AMR) AF: 0.598 AC: 9135 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2129 AN: 3466

East Asian (EAS) AF: 0.571 AC: 2945 AN: 5156

South Asian (SAS) AF: 0.589 AC: 2836 AN: 4812

European-Finnish (FIN) AF: 0.735 AC: 7777 AN: 10584

Middle Eastern (MID) AF: 0.592 AC: 173 AN: 292

European-Non Finnish (NFE) AF: 0.692 AC: 47046 AN: 67968

Other (OTH) AF: 0.625 AC: 1321 AN: 2114

Alfa AF: 0.650 Hom.: 12365

Bravo AF: 0.620

Asia WGS AF: 0.587 AC: 2040 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	3.8
DANN	Benign	0.81
PhyloP100		0.053
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: rs9587148; hg19: chr13-107158926;