12-15622852-C-A

Position:

• chr12-15622852-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004447.6(EPS8):​c.2355+306G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 151,686 control chromosomes in the GnomAD database, including 1,928 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (1928 hom., cov: 32)
• Consequence: EPS8 NM_004447.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.373

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 12-15622852-C-A is Benign according to our data. Variant chr12-15622852-C-A is described in ClinVar as [Benign]. Clinvar id is 1221592.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPS8	NM_004447.6	c.2355+306G>T		intron_variant		ENST00000281172.10	NP_004438.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPS8	ENST00000281172.10	c.2355+306G>T		intron_variant		1	NM_004447.6	ENSP00000281172	P1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21257 AN: 151596 Hom.: 1935 Cov.: 32

Gnomad AFR AF: 0.0416

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.140 AC: 21241 AN: 151686 Hom.: 1928 Cov.: 32 AF XY: 0.143 AC XY: 10564 AN XY: 74080

Gnomad4 AFR AF: 0.0415

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.275

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.177

Alfa AF: 0.103 Hom.: 217

Bravo AF: 0.135

Asia WGS AF: 0.171 AC: 593 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 09, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.78
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: rs12814229; hg19: chr12-15775786;