rs301927

Positions:

• chr3-97627774-G-A

Variant summary

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

The NM_001080448.3(EPHA6):​c.2575-10099G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 151,672 control chromosomes in the GnomAD database, including 38,844 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 0.68 (38844 hom., cov: 31)
• Consequence: EPHA6 NM_001080448.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0360

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHA6	NM_001080448.3	c.2575-10099G>A		intron_variant		ENST00000389672.10	NP_001073917.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHA6	ENST00000389672.10	c.2575-10099G>A		intron_variant		1	NM_001080448.3	ENSP00000374323	P1

Frequencies

GnomAD3 genomes AF: 0.685 AC: 103870 AN: 151556 Hom.: 38847 Cov.: 31

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.991

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.892

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.846

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.728

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

GnomAD4 genome AF: 0.685 AC: 103876 AN: 151672 Hom.: 38844 Cov.: 31 AF XY: 0.684 AC XY: 50701 AN XY: 74110

Gnomad4 AFR AF: 0.410

Gnomad4 AMR AF: 0.609

Gnomad4 ASJ AF: 0.892

Gnomad4 EAS AF: 0.353

Gnomad4 SAS AF: 0.744

Gnomad4 FIN AF: 0.846

Gnomad4 NFE AF: 0.849

Gnomad4 OTH AF: 0.723

Alfa AF: 0.815 Hom.: 65354

Bravo AF: 0.653

Asia WGS AF: 0.530 AC: 1845 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.52
DANN	Benign	0.48

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: rs301927; hg19: chr3-97346618;