rs9520087

Positions:

• chr13-106491972-G-A
• chr13-106491972-G-T

Variant summary

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

The NM_004093.4(EFNB2):​c.*1068C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 152,416 control chromosomes in the GnomAD database, including 18,656 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 0.49 (18621 hom., cov: 32)
  • Exomes 𝑓: 0.40 (35 hom.)
• Consequence: EFNB2 NM_004093.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFNB2	NM_004093.4	c.*1068C>T		3_prime_UTR_variant	5/5	ENST00000646441.1	NP_004084.1
EFNB2	NM_001372056.1	c.*1068C>T		3_prime_UTR_variant	4/4		NP_001358985.1
EFNB2	NM_001372057.1	c.*1068C>T		3_prime_UTR_variant	4/4		NP_001358986.1
EFNB2	XM_017020406.3	c.*1068C>T		3_prime_UTR_variant	5/5		XP_016875895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFNB2	ENST00000646441.1	c.*1068C>T		3_prime_UTR_variant	5/5		NM_004093.4	ENSP00000493716	P1
EFNB2	ENST00000643990.1	n.1674C>T		non_coding_transcript_exon_variant	4/4
	ENST00000649449.1	n.559+267G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74092 AN: 151838 Hom.: 18580 Cov.: 32

Gnomad AFR AF: 0.591

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.512

GnomAD4 exome AF: 0.396 AC: 182 AN: 460 Hom.: 35 Cov.: 0 AF XY: 0.397 AC XY: 112 AN XY: 282

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 0.386

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.667

GnomAD4 genome AF: 0.488 AC: 74191 AN: 151956 Hom.: 18621 Cov.: 32 AF XY: 0.487 AC XY: 36185 AN XY: 74248

Gnomad4 AFR AF: 0.592

Gnomad4 AMR AF: 0.482

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.625

Gnomad4 SAS AF: 0.574

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.515

Alfa AF: 0.457 Hom.: 16738

Bravo AF: 0.502

Asia WGS AF: 0.615 AC: 2142 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	0.074
DANN	Benign	0.76

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: rs9520087; hg19: chr13-107144320;