rs1458303

Positions:

• chr3-97449896-A-T

Variant summary

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

The NM_001080448.3(EPHA6):​c.1894+1166A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,080 control chromosomes in the GnomAD database, including 2,593 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 0.10 (2593 hom., cov: 32)
• Consequence: EPHA6 NM_001080448.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPHA6	NM_001080448.3	c.1894+1166A>T		intron_variant		ENST00000389672.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHA6	ENST00000389672.10	c.1894+1166A>T		intron_variant		1	NM_001080448.3	P1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15831 AN: 151962 Hom.: 2572 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0599

Gnomad ASJ AF: 0.0265

Gnomad EAS AF: 0.0139

Gnomad SAS AF: 0.00683

Gnomad FIN AF: 0.000848

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.00241

Gnomad OTH AF: 0.0891

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

GnomAD4 genome AF: 0.105 AC: 15902 AN: 152080 Hom.: 2593 Cov.: 32 AF XY: 0.101 AC XY: 7533 AN XY: 74366

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.0602

Gnomad4 ASJ AF: 0.0265

Gnomad4 EAS AF: 0.0137

Gnomad4 SAS AF: 0.00622

Gnomad4 FIN AF: 0.000848

Gnomad4 NFE AF: 0.00241

Gnomad4 OTH AF: 0.0882

Alfa AF: 0.0635 Hom.: 198

Bravo AF: 0.121

Asia WGS AF: 0.0480 AC: 165 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.66

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: rs1458303; hg19: chr3-97168740;