rs1887546

Positions:

• chr1-109753021-G-T

Variant summary

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

The NM_133181.4(EPS8L3):​c.1200+96C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 1,115,818 control chromosomes in the GnomAD database, including 53,958 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 0.36 (11242 hom., cov: 31)
  • Exomes 𝑓: 0.29 (42716 hom.)
• Consequence: EPS8L3 NM_133181.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.78

Genes affected

EPS8L3 (HGNC:21297): (EPS8 signaling adaptor L3) This gene encodes a protein that is related to epidermal growth factor receptor pathway substrate 8 (EPS8), a substrate for the epidermal growth factor receptor. The function of this protein is unknown. Alternatively spliced transcript variants encoding different isoforms exist. [provided by RefSeq, Jul 2008]

(HGNC:):

GSTM5 (HGNC:4637): (glutathione S-transferase mu 5) Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-transferase that belongs to the mu class. The mu class of enzymes functions in the detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, by conjugation with glutathione. The genes encoding the mu class of enzymes are organized in a gene cluster on chromosome 1p13.3 and are known to be highly polymorphic. These genetic variations can change an individual's susceptibility to carcinogens and toxins as well as affect the toxicity and efficacy of certain drugs. Diversification of these genes has occurred in regions encoding substrate-binding domains, as well as in tissue expression patterns, to accommodate an increasing number of foreign compounds. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPS8L3	NM_133181.4	c.1200+96C>A		intron_variant		ENST00000361965.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPS8L3	ENST00000361965.9	c.1200+96C>A		intron_variant		1	NM_133181.4	P4
	ENST00000431955.1	n.627+15880G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54779 AN: 151896 Hom.: 11214 Cov.: 31

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.0867

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.322

GnomAD4 exome AF: 0.289 AC: 278636 AN: 963804 Hom.: 42716 AF XY: 0.288 AC XY: 142396 AN XY: 494464

Gnomad4 AFR exome AF: 0.557

Gnomad4 AMR exome AF: 0.231

Gnomad4 ASJ exome AF: 0.333

Gnomad4 EAS exome AF: 0.0938

Gnomad4 SAS exome AF: 0.270

Gnomad4 FIN exome AF: 0.271

Gnomad4 NFE exome AF: 0.295

Gnomad4 OTH exome AF: 0.299

GnomAD4 genome AF: 0.361 AC: 54856 AN: 152014 Hom.: 11242 Cov.: 31 AF XY: 0.355 AC XY: 26374 AN XY: 74330

Gnomad4 AFR AF: 0.555

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.0863

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.321

Alfa AF: 0.317 Hom.: 4300

Bravo AF: 0.367

Asia WGS AF: 0.211 AC: 735 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.9
DANN	Benign	0.91

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: rs1887546; hg19: chr1-110295643; COSMIC: COSV62609395; COSMIC: COSV62609395;