rs12488683

Variant names:

• chr3-135136101-G-A
• rs12488683
• NM_004441.5:c.1297+3052G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-135136101-G-A
• chr3-135136101-G-T

Variant summary

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

The NM_004441.5(EPHB1):​c.1297+3052G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,140 control chromosomes in the GnomAD database, including 7,018 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 0.30 (7018 hom., cov: 32)
• Consequence: EPHB1 NM_004441.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.260
• Publications: 1 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.354 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.1297+3052G>A		intron	N/A	NP_004432.1	P54762-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHB1	ENST00000398015.8	TSL:1 MANE Select	c.1297+3052G>A		intron	N/A	ENSP00000381097.3	P54762-1
	EPHB1	ENST00000647596.1		c.1297+3052G>A		intron	N/A	ENSP00000497153.1	A0A3B3IRY8
	EPHB1	ENST00000970111.1		c.1297+3052G>A		intron	N/A	ENSP00000640170.1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45469 AN: 152022 Hom.: 7012 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.293

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.299 AC: 45485 AN: 152140 Hom.: 7018 Cov.: 32 AF XY: 0.299 AC XY: 22231 AN XY: 74382

African (AFR) AF: 0.258 AC: 10682 AN: 41472

American (AMR) AF: 0.253 AC: 3876 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1292 AN: 3470

East Asian (EAS) AF: 0.155 AC: 801 AN: 5170

South Asian (SAS) AF: 0.369 AC: 1779 AN: 4826

European-Finnish (FIN) AF: 0.310 AC: 3279 AN: 10590

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.335 AC: 22751 AN: 68004

Other (OTH) AF: 0.289 AC: 611 AN: 2114

Alfa AF: 0.320 Hom.: 34241

Bravo AF: 0.291

Asia WGS AF: 0.241 AC: 841 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.0
DANN	Benign	0.17
PhyloP100		0.26
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: rs12488683; hg19: chr3-134854943;