3-134951682-C-T

Variant names:

• chr3-134951682-C-T
• rs7644369
• NM_004441.5:c.435C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_004441.5(EPHB1):​c.435C>T​(p.Ser145Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 1,613,704 control chromosomes in the GnomAD database, including 169,132 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 (18871 hom., cov: 31)
  • Exomes 𝑓: 0.45 (150261 hom.)
• Consequence: EPHB1 NM_004441.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.30
• Publications: 20 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP7: Synonymous conserved (PhyloP=2.3 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.601 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHB1	NM_004441.5	MANE Select	c.435C>T	p.Ser145Ser	synonymous	Exon 3 of 16	NP_004432.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHB1	ENST00000398015.8	TSL:1 MANE Select	c.435C>T	p.Ser145Ser	synonymous	Exon 3 of 16	ENSP00000381097.3
	EPHB1	ENST00000482618.5	TSL:1	n.435C>T		non_coding_transcript_exon	Exon 3 of 6	ENSP00000420338.1
	EPHB1	ENST00000488154.5	TSL:1	n.435C>T		non_coding_transcript_exon	Exon 3 of 5

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74164 AN: 151746 Hom.: 18866 Cov.: 31

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.503

GnomAD2 exomes AF: 0.459 AC: 114413 AN: 249416 AF XY: 0.458

Gnomad AFR exome AF: 0.614

Gnomad AMR exome AF: 0.523

Gnomad ASJ exome AF: 0.540

Gnomad EAS exome AF: 0.194

Gnomad FIN exome AF: 0.354

Gnomad NFE exome AF: 0.454

Gnomad OTH exome AF: 0.470

GnomAD4 exome AF: 0.449 AC: 656608 AN: 1461838 Hom.: 150261 Cov.: 68 AF XY: 0.450 AC XY: 327507 AN XY: 727214

African (AFR) AF: 0.627 AC: 20978 AN: 33478

American (AMR) AF: 0.523 AC: 23369 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 14082 AN: 26136

East Asian (EAS) AF: 0.159 AC: 6302 AN: 39698

South Asian (SAS) AF: 0.519 AC: 44806 AN: 86258

European-Finnish (FIN) AF: 0.359 AC: 19203 AN: 53416

Middle Eastern (MID) AF: 0.564 AC: 3254 AN: 5768

European-Non Finnish (NFE) AF: 0.447 AC: 497011 AN: 1111974

Other (OTH) AF: 0.457 AC: 27603 AN: 60388

GnomAD4 genome AF: 0.489 AC: 74210 AN: 151866 Hom.: 18871 Cov.: 31 AF XY: 0.483 AC XY: 35820 AN XY: 74232

African (AFR) AF: 0.607 AC: 25103 AN: 41362

American (AMR) AF: 0.518 AC: 7908 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 1825 AN: 3470

East Asian (EAS) AF: 0.198 AC: 1027 AN: 5178

South Asian (SAS) AF: 0.519 AC: 2497 AN: 4808

European-Finnish (FIN) AF: 0.343 AC: 3623 AN: 10560

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.451 AC: 30612 AN: 67908

Other (OTH) AF: 0.503 AC: 1060 AN: 2106

Alfa AF: 0.473 Hom.: 56761

Bravo AF: 0.507

Asia WGS AF: 0.428 AC: 1488 AN: 3478

EpiCase AF: 0.458

EpiControl AF: 0.469

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	11
DANN	Benign	0.69
PhyloP100		2.3
Mutation Taster		=95/5	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: rs7644369; hg19: chr3-134670524; COSMIC: COSV67660842; COSMIC: COSV67660842;