1-109750234-G-C

Variant names:

• chr1-109750234-G-C
• rs15864
• NM_133181.4:c.*157C>G

Variant summary

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

The NM_133181.4(EPS8L3):​c.*157C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 841,270 control chromosomes in the GnomAD database, including 47,647 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 0.26 (6683 hom., cov: 32)
  • Exomes 𝑓: 0.33 (40964 hom.)
• Consequence: EPS8L3 NM_133181.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85
• Publications: 16 publications found

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]

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]

ENSG00000241720 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133181.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPS8L3	NM_133181.4	MANE Select	c.*157C>G		3_prime_UTR	Exon 19 of 19	NP_573444.2
	EPS8L3	NM_139053.3		c.*157C>G		3_prime_UTR	Exon 19 of 19	NP_620641.1
	EPS8L3	NM_024526.4		c.*157C>G		3_prime_UTR	Exon 19 of 19	NP_078802.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPS8L3	ENST00000361965.9	TSL:1 MANE Select	c.*157C>G		3_prime_UTR	Exon 19 of 19	ENSP00000355255.4
	EPS8L3	ENST00000369805.7	TSL:1	c.*157C>G		3_prime_UTR	Exon 19 of 19	ENSP00000358820.3
	EPS8L3	ENST00000361852.8	TSL:1	c.*157C>G		3_prime_UTR	Exon 19 of 19	ENSP00000354551.4

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38927 AN: 151944 Hom.: 6683 Cov.: 32

Gnomad AFR AF: 0.0651

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.741

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.271

GnomAD4 exome AF: 0.327 AC: 225256 AN: 689208 Hom.: 40964 Cov.: 9 AF XY: 0.331 AC XY: 117454 AN XY: 355348

African (AFR) AF: 0.0568 AC: 973 AN: 17138

American (AMR) AF: 0.413 AC: 10805 AN: 26180

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 4842 AN: 16894

East Asian (EAS) AF: 0.718 AC: 23185 AN: 32298

South Asian (SAS) AF: 0.395 AC: 21481 AN: 54438

European-Finnish (FIN) AF: 0.290 AC: 13147 AN: 45336

Middle Eastern (MID) AF: 0.253 AC: 690 AN: 2732

European-Non Finnish (NFE) AF: 0.303 AC: 139366 AN: 460228

Other (OTH) AF: 0.317 AC: 10767 AN: 33964

GnomAD4 genome AF: 0.256 AC: 38932 AN: 152062 Hom.: 6683 Cov.: 32 AF XY: 0.261 AC XY: 19368 AN XY: 74334

African (AFR) AF: 0.0650 AC: 2702 AN: 41554

American (AMR) AF: 0.334 AC: 5109 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1006 AN: 3472

East Asian (EAS) AF: 0.740 AC: 3805 AN: 5142

South Asian (SAS) AF: 0.394 AC: 1888 AN: 4790

European-Finnish (FIN) AF: 0.288 AC: 3038 AN: 10556

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.303 AC: 20583 AN: 67956

Other (OTH) AF: 0.275 AC: 580 AN: 2110

Alfa AF: 0.267 Hom.: 795

Bravo AF: 0.252

Asia WGS AF: 0.493 AC: 1712 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.013
DANN	Benign	0.78
PhyloP100		-1.9
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: rs15864; hg19: chr1-110292856; COSMIC: COSV62609033; COSMIC: COSV62609033;