13-106519927-A-G

Variant names:

• chr13-106519927-A-G
• rs2391336
• NM_004093.4:c.123-7115T>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.123-7115T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 152,006 control chromosomes in the GnomAD database, including 22,187 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 0.53 (22187 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: EFNB2 NM_004093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.314
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.588 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.123-7115T>C		intron	N/A	NP_004084.1
	EFNB2	NM_001372056.1		c.123-7115T>C		intron	N/A	NP_001358985.1
	EFNB2	NM_001372057.1		c.123-7115T>C		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.123-7115T>C		intron	N/A	ENSP00000493716.1
	ENSG00000284966	ENST00000646480.1		n.4291A>G		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80728 AN: 151888 Hom.: 22184 Cov.: 33

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.523

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

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) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.531 AC: 80763 AN: 152006 Hom.: 22187 Cov.: 33 AF XY: 0.536 AC XY: 39812 AN XY: 74290

African (AFR) AF: 0.389 AC: 16126 AN: 41448

American (AMR) AF: 0.542 AC: 8275 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 1702 AN: 3470

East Asian (EAS) AF: 0.602 AC: 3108 AN: 5164

South Asian (SAS) AF: 0.541 AC: 2609 AN: 4824

European-Finnish (FIN) AF: 0.647 AC: 6833 AN: 10560

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.593 AC: 40291 AN: 67952

Other (OTH) AF: 0.521 AC: 1098 AN: 2108

Alfa AF: 0.566 Hom.: 100247

Bravo AF: 0.517

Asia WGS AF: 0.545 AC: 1892 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.5
DANN	Benign	0.65
PhyloP100		0.31
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: rs2391336; hg19: chr13-107172275;