rs649593

chr1-37741891-C-T

Variant summary

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

The NM_001099439.2(EPHA10):c.1358-6501G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 150,008 control chromosomes in the GnomAD database, including 8,475 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 0.33 (8475 hom., cov: 31)
• Consequence: EPHA10 NM_001099439.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98

Genes affected

EPHA10 (HGNC:19987): (EPH receptor A10) Ephrin receptors, the largest subfamily of receptor tyrosine kinases (RTKs), and their ephrin ligands are important mediators of cell-cell communication regulating cell attachment, shape, and mobility in neuronal and epithelial cells (Aasheim et al., 2005 [PubMed 15777695]). See MIM 179610 for additional background on Eph receptors and ephrins.[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPHA10	NM_001099439.2	c.1358-6501G>A		intron_variant		ENST00000373048.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHA10	ENST00000373048.9	c.1358-6501G>A		intron_variant		5	NM_001099439.2	P1

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50207 AN: 149892 Hom.: 8466 Cov.: 31

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.356

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

GnomAD4 genome AF: 0.335 AC: 50249 AN: 150008 Hom.: 8475 Cov.: 31 AF XY: 0.337 AC XY: 24708 AN XY: 73348

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.394

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.478

Gnomad4 SAS AF: 0.400

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.337

Gnomad4 OTH AF: 0.364

Alfa AF: 0.343 Hom.: 1430

Bravo AF: 0.340

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	0.52
Dann	Benign	0.91

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: rs649593; hg19: chr1-38207563; COSMIC: COSV57622531; COSMIC: COSV57622531;