7-142864981-C-T

Variant names:

• chr7-142864981-C-T
• rs6947538
• NM_004445.6:c.949+232C>T

Variant summary

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

The NM_004445.6(EPHB6):​c.949+232C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 152,186 control chromosomes in the GnomAD database, including 48,098 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 0.76 (48098 hom., cov: 33)
• Consequence: EPHB6 NM_004445.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40
• Publications: 5 publications found

Genes affected

EPHB6 (HGNC:3396): (EPH receptor B6) This gene encodes a member of a family of transmembrane proteins that function as receptors for ephrin-B family proteins. Unlike other members of this family, the encoded protein does not contain a functional kinase domain. Activity of this protein can influence cell adhesion and migration. Expression of this gene is downregulated during tumor progression, suggesting that the protein may suppress tumor invasion and metastasis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHB6	NM_004445.6	c.949+232C>T		intron_variant	Intron 7 of 19	ENST00000652003.1	NP_004436.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHB6	ENST00000652003.1	c.949+232C>T		intron_variant	Intron 7 of 19		NM_004445.6	ENSP00000498670.1

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115767 AN: 152068 Hom.: 48089 Cov.: 33

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.918

Gnomad AMR AF: 0.858

Gnomad ASJ AF: 0.898

Gnomad EAS AF: 0.969

Gnomad SAS AF: 0.890

Gnomad FIN AF: 0.891

Gnomad MID AF: 0.879

Gnomad NFE AF: 0.909

Gnomad OTH AF: 0.781

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

GnomAD4 genome AF: 0.761 AC: 115797 AN: 152186 Hom.: 48098 Cov.: 33 AF XY: 0.767 AC XY: 57070 AN XY: 74432

African (AFR) AF: 0.390 AC: 16164 AN: 41460

American (AMR) AF: 0.859 AC: 13136 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.898 AC: 3115 AN: 3470

East Asian (EAS) AF: 0.969 AC: 5026 AN: 5188

South Asian (SAS) AF: 0.890 AC: 4294 AN: 4824

European-Finnish (FIN) AF: 0.891 AC: 9455 AN: 10612

Middle Eastern (MID) AF: 0.880 AC: 257 AN: 292

European-Non Finnish (NFE) AF: 0.909 AC: 61857 AN: 68018

Other (OTH) AF: 0.783 AC: 1656 AN: 2114

Alfa AF: 0.872 Hom.: 96120

Bravo AF: 0.742

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.023
PhyloP100		-2.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6947538; hg19: chr7-142562736;