rs10505786

Positions:

• chr12-15708037-G-C

Variant summary

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

The NM_004447.6(EPS8):​c.-21-25065C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,138 control chromosomes in the GnomAD database, including 2,868 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 0.17 (2868 hom., cov: 32)
• Consequence: EPS8 NM_004447.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.228

Genes affected

EPS8 (HGNC:3420): (EGFR pathway substrate 8, signaling adaptor) This gene encodes a member of the EPS8 family. This protein contains one PH domain and one SH3 domain. It functions as part of the EGFR pathway, though its exact role has not been determined. Highly similar proteins in other organisms are involved in the transduction of signals from Ras to Rac and growth factor-mediated actin remodeling. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPS8	NM_004447.6	c.-21-25065C>G		intron_variant		ENST00000281172.10	NP_004438.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPS8	ENST00000281172.10	c.-21-25065C>G		intron_variant		1	NM_004447.6	ENSP00000281172.5

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26454 AN: 152020 Hom.: 2862 Cov.: 32

Gnomad AFR AF: 0.0849

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.174 AC: 26465 AN: 152138 Hom.: 2868 Cov.: 32 AF XY: 0.177 AC XY: 13141 AN XY: 74360

Gnomad4 AFR AF: 0.0847

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.205

Alfa AF: 0.184 Hom.: 366

Bravo AF: 0.184

Asia WGS AF: 0.119 AC: 414 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.53
DANN	Benign	0.40

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: rs10505786; hg19: chr12-15860971;