13-106517693-C-T

Position:

• chr13-106517693-C-T

Variant summary

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

The NM_004093.4(EFNB2):​c.123-4881G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 152,104 control chromosomes in the GnomAD database, including 42,912 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 0.75 (42909 hom., cov: 32)
  • Exomes 𝑓: 0.88 (3 hom.)
• Consequence: EFNB2 NM_004093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFNB2	NM_004093.4	c.123-4881G>A		intron_variant		ENST00000646441.1	NP_004084.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFNB2	ENST00000646441.1	c.123-4881G>A		intron_variant			NM_004093.4	ENSP00000493716.1
ENSG00000284966	ENST00000646480.1	n.2057C>T		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes AF: 0.751 AC: 114075 AN: 151978 Hom.: 42865 Cov.: 32

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.871

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.725

Gnomad SAS AF: 0.776

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.757

GnomAD4 exome AF: 0.875 AC: 7 AN: 8 Hom.: 3 Cov.: 0 AF XY: 0.833 AC XY: 5 AN XY: 6

Gnomad4 NFE exome AF: 0.875

GnomAD4 genome AF: 0.751 AC: 114176 AN: 152096 Hom.: 42909 Cov.: 32 AF XY: 0.753 AC XY: 55958 AN XY: 74356

Gnomad4 AFR AF: 0.744

Gnomad4 AMR AF: 0.736

Gnomad4 ASJ AF: 0.734

Gnomad4 EAS AF: 0.724

Gnomad4 SAS AF: 0.777

Gnomad4 FIN AF: 0.764

Gnomad4 NFE AF: 0.755

Gnomad4 OTH AF: 0.757

Alfa AF: 0.747 Hom.: 23869

Bravo AF: 0.747

Asia WGS AF: 0.756 AC: 2630 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.8
DANN	Benign	0.68

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: rs9514545; hg19: chr13-107170041;