rs6801975

Positions:

• chr3-97472495-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080448.3(EPHA6):​c.1895-2857C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 151,646 control chromosomes in the GnomAD database, including 2,182 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 0.15 (2182 hom., cov: 32)
• Consequence: EPHA6 NM_001080448.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660

Genes affected

EPHA6 (HGNC:19296): (EPH receptor A6) Predicted to enable transmembrane-ephrin receptor activity. Predicted to be involved in axon guidance; positive regulation of kinase activity; and transmembrane receptor protein tyrosine kinase signaling pathway. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPHA6	NM_001080448.3	c.1895-2857C>T		intron_variant		ENST00000389672.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHA6	ENST00000389672.10	c.1895-2857C>T		intron_variant		1	NM_001080448.3	P1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22346 AN: 151528 Hom.: 2176 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.0894

Gnomad FIN AF: 0.0861

Gnomad MID AF: 0.0605

Gnomad NFE AF: 0.0926

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.148 AC: 22384 AN: 151646 Hom.: 2182 Cov.: 32 AF XY: 0.148 AC XY: 10939 AN XY: 74132

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.0386

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.0879

Gnomad4 FIN AF: 0.0861

Gnomad4 NFE AF: 0.0926

Gnomad4 OTH AF: 0.130

Alfa AF: 0.105 Hom.: 1203

Bravo AF: 0.165

Asia WGS AF: 0.132 AC: 460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.6
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs6801975; hg19: chr3-97191339;