rs649593

Variant names:

• chr1-37741891-C-T
• rs649593
• NM_001099439.2:c.1358-6501G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

EPHA10 Gene-Disease associations (from GenCC):

• hearing loss, autosomal dominant 88

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
EPHA10	NM_001099439.2	c.1358-6501G>A		intron_variant	Intron 5 of 16	ENST00000373048.9	NP_001092909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHA10	ENST00000373048.9	c.1358-6501G>A		intron_variant	Intron 5 of 16	5	NM_001099439.2	ENSP00000362139.4

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

African (AFR) AF: 0.272 AC: 10768 AN: 39588

American (AMR) AF: 0.394 AC: 6011 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1579 AN: 3464

East Asian (EAS) AF: 0.478 AC: 2469 AN: 5166

South Asian (SAS) AF: 0.400 AC: 1916 AN: 4796

European-Finnish (FIN) AF: 0.304 AC: 3201 AN: 10522

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22920 AN: 67938

Other (OTH) AF: 0.364 AC: 762 AN: 2096

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
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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