12-15621303-TACAA-T

Position:

• chr12-15621303-TACAA-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP6_Moderate BS1

The ENST00000281172.10(EPS8):​c.*10_*13del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000443 in 1,422,896 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000035 (0 hom.)
• Consequence: EPS8 ENST00000281172.10 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 1.37

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 12-15621303-TACAA-T is Benign according to our data. Variant chr12-15621303-TACAA-T is described in ClinVar as [Likely_benign]. Clinvar id is 1254677.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000118 (18/152118) while in subpopulation AFR AF= 0.000193 (8/41432). AF 95% confidence interval is 0.0000957. There are 0 homozygotes in gnomad4. There are 11 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPS8	NM_004447.6	c.*10_*13del		3_prime_UTR_variant	21/21	ENST00000281172.10	NP_004438.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPS8	ENST00000281172.10	c.*10_*13del		3_prime_UTR_variant	21/21	1	NM_004447.6	ENSP00000281172	P1

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152118 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.0000331 AC: 7 AN: 211756 Hom.: 0 AF XY: 0.0000260 AC XY: 3 AN XY: 115548

Gnomad AFR exome AF: 0.000149

Gnomad AMR exome AF: 0.0000409

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000491

Gnomad NFE exome AF: 0.0000198

Gnomad OTH exome AF: 0.000205

GnomAD4 exome AF: 0.0000354 AC: 45 AN: 1270778 Hom.: 0 AF XY: 0.0000281 AC XY: 18 AN XY: 639746

Gnomad4 AFR exome AF: 0.000145

Gnomad4 AMR exome AF: 0.0000861

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000192

Gnomad4 NFE exome AF: 0.0000364

Gnomad4 OTH exome AF: 0.0000372

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152118 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74320

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.000479

Bravo AF: 0.000110

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

EPS8-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 21, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 24, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs749312796; hg19: chr12-15774237;