3-134796494-T-G

Variant names:

• chr3-134796494-T-G
• rs3732568
• NM_004441.5:c.58+805T>G

Variant summary

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

The NM_004441.5(EPHB1):​c.58+805T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 152,236 control chromosomes in the GnomAD database, including 43,449 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 0.71 (43439 hom., cov: 34)
  • Exomes 𝑓: 0.86 (10 hom.)
• Consequence: EPHB1 NM_004441.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132
• Publications: 4 publications found

Genes affected

EPHB1 (HGNC:3392): (EPH receptor B1) Ephrin receptors and their ligands, the ephrins, mediate numerous developmental processes, particularly in the nervous system. 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. The Eph family of receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. Ephrin receptors make up the largest subgroup of the receptor tyrosine kinase (RTK) family. The protein encoded by this gene is a receptor for ephrin-B family members. [provided by RefSeq, Jul 2008]

ENSG00000288700 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004441.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHB1	NM_004441.5	MANE Select	c.58+805T>G		intron	N/A	NP_004432.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHB1	ENST00000398015.8	TSL:1 MANE Select	c.58+805T>G		intron	N/A	ENSP00000381097.3
	EPHB1	ENST00000482618.5	TSL:1	n.58+805T>G		intron	N/A	ENSP00000420338.1
	EPHB1	ENST00000488154.5	TSL:1	n.58+805T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.712 AC: 108271 AN: 152090 Hom.: 43451 Cov.: 34

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.779

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.851

Gnomad EAS AF: 0.902

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.908

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.888

Gnomad OTH AF: 0.765

GnomAD4 exome AF: 0.857 AC: 24 AN: 28 Hom.: 10 AF XY: 0.875 AC XY: 21 AN XY: 24

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 0.750 AC: 3 AN: 4

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: 0.950 AC: 19 AN: 20

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.711 AC: 108270 AN: 152208 Hom.: 43439 Cov.: 34 AF XY: 0.713 AC XY: 53039 AN XY: 74426

African (AFR) AF: 0.310 AC: 12884 AN: 41528

American (AMR) AF: 0.807 AC: 12338 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.851 AC: 2952 AN: 3470

East Asian (EAS) AF: 0.901 AC: 4640 AN: 5148

South Asian (SAS) AF: 0.599 AC: 2891 AN: 4824

European-Finnish (FIN) AF: 0.908 AC: 9643 AN: 10622

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.888 AC: 60360 AN: 68000

Other (OTH) AF: 0.764 AC: 1616 AN: 2114

Alfa AF: 0.832 Hom.: 58974

Bravo AF: 0.690

Asia WGS AF: 0.699 AC: 2432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.4
DANN	Benign	0.51
PhyloP100		-0.13
PromoterAI		-0.029	Neutral
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: rs3732568; hg19: chr3-134515336;