rs7612669

Positions:

• chr3-97060482-A-G

Variant summary

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

The NM_001080448.3(EPHA6):​c.1114+72489A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,146 control chromosomes in the GnomAD database, including 2,730 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 0.14 (2730 hom., cov: 31)
• Consequence: EPHA6 NM_001080448.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPHA6	NM_001080448.3	c.1114+72489A>G		intron_variant		ENST00000389672.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHA6	ENST00000389672.10	c.1114+72489A>G		intron_variant		1	NM_001080448.3	P1
EPHA6	ENST00000470610.6	c.1114+72489A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21738 AN: 152028 Hom.: 2718 Cov.: 31

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0914

Gnomad ASJ AF: 0.0974

Gnomad EAS AF: 0.0334

Gnomad SAS AF: 0.0814

Gnomad FIN AF: 0.0532

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.0641

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.143 AC: 21784 AN: 152146 Hom.: 2730 Cov.: 31 AF XY: 0.139 AC XY: 10358 AN XY: 74396

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.0913

Gnomad4 ASJ AF: 0.0974

Gnomad4 EAS AF: 0.0334

Gnomad4 SAS AF: 0.0812

Gnomad4 FIN AF: 0.0532

Gnomad4 NFE AF: 0.0641

Gnomad4 OTH AF: 0.146

Alfa AF: 0.0824 Hom.: 390

Bravo AF: 0.154

Asia WGS AF: 0.0960 AC: 335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.45

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: rs7612669; hg19: chr3-96779326;