1-37725866-T-C

Variant names:

• chr1-37725866-T-C
• rs7541350
• NM_001099439.2:c.1772+1236A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001099439.2(EPHA10):​c.1772+1236A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0942 in 152,098 control chromosomes in the GnomAD database, including 720 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 0.094 (720 hom., cov: 32)
• Consequence: EPHA10 NM_001099439.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.93
• Publications: 7 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHA10	NM_001099439.2	c.1772+1236A>G		intron_variant	Intron 8 of 16	ENST00000373048.9	NP_001092909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHA10	ENST00000373048.9	c.1772+1236A>G		intron_variant	Intron 8 of 16	5	NM_001099439.2	ENSP00000362139.4
EPHA10	ENST00000432874.7	n.191+1236A>G		intron_variant	Intron 2 of 15	5		ENSP00000436425.1

Frequencies

GnomAD3 genomes AF: 0.0942 AC: 14318 AN: 151980 Hom.: 717 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.0861

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0228

Gnomad SAS AF: 0.0416

Gnomad FIN AF: 0.0663

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0918

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.0942 AC: 14325 AN: 152098 Hom.: 720 Cov.: 32 AF XY: 0.0908 AC XY: 6753 AN XY: 74360

African (AFR) AF: 0.119 AC: 4955 AN: 41496

American (AMR) AF: 0.0859 AC: 1313 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 424 AN: 3468

East Asian (EAS) AF: 0.0226 AC: 117 AN: 5172

South Asian (SAS) AF: 0.0409 AC: 197 AN: 4822

European-Finnish (FIN) AF: 0.0663 AC: 702 AN: 10582

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.0918 AC: 6241 AN: 67962

Other (OTH) AF: 0.109 AC: 230 AN: 2112

Alfa AF: 0.0929 Hom.: 365

Bravo AF: 0.0982

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.071
DANN	Benign	0.34
PhyloP100		-2.9
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: rs7541350; hg19: chr1-38191538; COSMIC: COSV57622332; COSMIC: COSV57622332;