chr3-135193075-A-G

Variant names:

• chr3-135193075-A-G
• rs6776570
• NM_004441.5:c.2130+252A>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.2130+252A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 152,012 control chromosomes in the GnomAD database, including 17,748 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 0.47 (17748 hom., cov: 32)
• Consequence: EPHB1 NM_004441.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• 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]

ENSG00000240086 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHB1	NM_004441.5	c.2130+252A>G		intron_variant	Intron 11 of 15	ENST00000398015.8	NP_004432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHB1	ENST00000398015.8	c.2130+252A>G		intron_variant	Intron 11 of 15	1	NM_004441.5	ENSP00000381097.3
EPHB1	ENST00000647596.1	c.2130+252A>G		intron_variant	Intron 11 of 15			ENSP00000497153.1
EPHB1	ENST00000493838.1	c.813+252A>G		intron_variant	Intron 9 of 13	2		ENSP00000419574.1
ENSG00000240086	ENST00000649588.1	n.329-34747T>C		intron_variant	Intron 3 of 6

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71592 AN: 151894 Hom.: 17737 Cov.: 32

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.524

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.471 AC: 71651 AN: 152012 Hom.: 17748 Cov.: 32 AF XY: 0.473 AC XY: 35113 AN XY: 74302

African (AFR) AF: 0.608 AC: 25181 AN: 41442

American (AMR) AF: 0.489 AC: 7478 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1140 AN: 3468

East Asian (EAS) AF: 0.633 AC: 3266 AN: 5160

South Asian (SAS) AF: 0.523 AC: 2519 AN: 4814

European-Finnish (FIN) AF: 0.335 AC: 3542 AN: 10572

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.399 AC: 27134 AN: 67952

Other (OTH) AF: 0.446 AC: 941 AN: 2108

Alfa AF: 0.414 Hom.: 16879

Bravo AF: 0.485

Asia WGS AF: 0.579 AC: 2012 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.30
DANN	Benign	0.88
PhyloP100		-1.5
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: rs6776570; hg19: chr3-134911917;