13-106516301-C-G

Position:

• chr13-106516301-C-G

Variant summary

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

The NM_004093.4(EFNB2):​c.123-3489G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 152,096 control chromosomes in the GnomAD database, including 43,900 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 0.76 (43899 hom., cov: 31)
  • Exomes 𝑓: 0.67 (1 hom.)
• Consequence: EFNB2 NM_004093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.68

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFNB2	NM_004093.4	c.123-3489G>C		intron_variant		ENST00000646441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFNB2	ENST00000646441.1	c.123-3489G>C		intron_variant			NM_004093.4	P1
	ENST00000646480.1	n.665C>G		non_coding_transcript_exon_variant	3/3
EFNB2	ENST00000643990.1	n.10+137G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115401 AN: 151972 Hom.: 43869 Cov.: 31

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.871

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.747

Gnomad SAS AF: 0.780

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.771

GnomAD4 exome AF: 0.667 AC: 4 AN: 6 Hom.: 1 Cov.: 0 AF XY: 0.750 AC XY: 3 AN XY: 4

Gnomad4 NFE exome AF: 0.750

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.759 AC: 115485 AN: 152090 Hom.: 43899 Cov.: 31 AF XY: 0.761 AC XY: 56549 AN XY: 74332

Gnomad4 AFR AF: 0.738

Gnomad4 AMR AF: 0.748

Gnomad4 ASJ AF: 0.747

Gnomad4 EAS AF: 0.747

Gnomad4 SAS AF: 0.781

Gnomad4 FIN AF: 0.773

Gnomad4 NFE AF: 0.771

Gnomad4 OTH AF: 0.771

Alfa AF: 0.705 Hom.: 2120

Bravo AF: 0.756

Asia WGS AF: 0.758 AC: 2637 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.021
DANN	Benign	0.51

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: rs7320751; hg19: chr13-107168649;