1-109760883-C-T

Position:

• chr1-109760883-C-T

Variant summary

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

The NM_133181.4(EPS8L3):​c.96+612G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,030 control chromosomes in the GnomAD database, including 6,983 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 0.27 (6983 hom., cov: 31)
• Consequence: EPS8L3 NM_133181.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.936

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPS8L3	NM_133181.4	c.96+612G>A		intron_variant		ENST00000361965.9	NP_573444.2
LOC124904258	XR_007066303.1	n.86+933C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPS8L3	ENST00000361965.9	c.96+612G>A		intron_variant		1	NM_133181.4	ENSP00000355255	P4
	ENST00000431955.1	n.628-14189C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41140 AN: 151910 Hom.: 6988 Cov.: 31

Gnomad AFR AF: 0.0737

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.271 AC: 41133 AN: 152030 Hom.: 6983 Cov.: 31 AF XY: 0.272 AC XY: 20198 AN XY: 74270

Gnomad4 AFR AF: 0.0736

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.625

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.278

Alfa AF: 0.307 Hom.: 5155

Bravo AF: 0.261

Asia WGS AF: 0.445 AC: 1548 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.94
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4970779; hg19: chr1-110303505;