rs17464981

Variant names:

• chr1-37726865-T-C
• rs17464981
• NM_001099439.2:c.1772+237A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001099439.2(EPHA10):​c.1772+237A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0685 in 152,312 control chromosomes in the GnomAD database, including 459 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 0.069 (459 hom., cov: 33)
• Consequence: EPHA10 NM_001099439.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74
• Publications: 6 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.091 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099439.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHA10	NM_001099439.2	MANE Select	c.1772+237A>G		intron	N/A	NP_001092909.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHA10	ENST00000373048.9	TSL:5 MANE Select	c.1772+237A>G		intron	N/A	ENSP00000362139.4
	EPHA10	ENST00000432874.7	TSL:5	n.191+237A>G		intron	N/A	ENSP00000436425.1
	EPHA10	ENST00000437645.5	TSL:1	n.446+237A>G		intron	N/A	ENSP00000432693.1

Frequencies

GnomAD3 genomes AF: 0.0686 AC: 10441 AN: 152194 Hom.: 459 Cov.: 33

Gnomad AFR AF: 0.0290

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0731

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.0222

Gnomad SAS AF: 0.0347

Gnomad FIN AF: 0.0678

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.0929

Gnomad OTH AF: 0.0926

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

GnomAD4 genome AF: 0.0685 AC: 10438 AN: 152312 Hom.: 459 Cov.: 33 AF XY: 0.0660 AC XY: 4918 AN XY: 74480

African (AFR) AF: 0.0290 AC: 1207 AN: 41572

American (AMR) AF: 0.0729 AC: 1116 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 446 AN: 3472

East Asian (EAS) AF: 0.0221 AC: 114 AN: 5166

South Asian (SAS) AF: 0.0344 AC: 166 AN: 4832

European-Finnish (FIN) AF: 0.0678 AC: 720 AN: 10620

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.0929 AC: 6321 AN: 68028

Other (OTH) AF: 0.0917 AC: 194 AN: 2116

Alfa AF: 0.0855 Hom.: 341

Bravo AF: 0.0689

Asia WGS AF: 0.0210 AC: 75 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	18
DANN	Benign	0.83
PhyloP100		1.7
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: rs17464981; hg19: chr1-38192537; COSMIC: COSV57622371; COSMIC: COSV57622371;