chr13-106517046-G-A

Variant names:

• chr13-106517046-G-A
• rs4772795
• NM_004093.4:c.123-4234C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004093.4(EFNB2):​c.123-4234C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 152,048 control chromosomes in the GnomAD database, including 41,985 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 0.74 (41985 hom., cov: 32)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: EFNB2 NM_004093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930
• 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]

ENSG00000284966 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004093.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFNB2	NM_004093.4	MANE Select	c.123-4234C>T		intron	N/A	NP_004084.1
	EFNB2	NM_001372056.1		c.123-4234C>T		intron	N/A	NP_001358985.1
	EFNB2	NM_001372057.1		c.123-4234C>T		intron	N/A	NP_001358986.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFNB2	ENST00000646441.1	MANE Select	c.123-4234C>T		intron	N/A	ENSP00000493716.1
	ENSG00000284966	ENST00000646480.1		n.1410G>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112687 AN: 151924 Hom.: 41954 Cov.: 32

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.871

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.746

Gnomad EAS AF: 0.732

Gnomad SAS AF: 0.779

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.761

GnomAD4 exome AF: 0.167 AC: 1 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

African (AFR) AF: 0.00 AC: 0 AN: 2

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: 0.250 AC: 1 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.742 AC: 112770 AN: 152042 Hom.: 41985 Cov.: 32 AF XY: 0.744 AC XY: 55292 AN XY: 74316

African (AFR) AF: 0.683 AC: 28286 AN: 41444

American (AMR) AF: 0.740 AC: 11311 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.746 AC: 2590 AN: 3472

East Asian (EAS) AF: 0.731 AC: 3761 AN: 5144

South Asian (SAS) AF: 0.779 AC: 3757 AN: 4820

European-Finnish (FIN) AF: 0.774 AC: 8186 AN: 10576

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.769 AC: 52265 AN: 67990

Other (OTH) AF: 0.760 AC: 1606 AN: 2112

Alfa AF: 0.760 Hom.: 83623

Bravo AF: 0.734

Asia WGS AF: 0.748 AC: 2604 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.79
DANN	Benign	0.40
PhyloP100		0.093
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: rs4772795; hg19: chr13-107169394;