chr1-109753021-G-T

Variant names:

• chr1-109753021-G-T
• rs1887546
• NM_133181.4:c.1200+96C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 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=-0.69).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.549 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPS8L3	NM_133181.4	MANE Select	c.1200+96C>A		intron	N/A	NP_573444.2
	EPS8L3	NM_139053.3		c.1203+96C>A		intron	N/A	NP_620641.1
	EPS8L3	NM_024526.4		c.1200+96C>A		intron	N/A	NP_078802.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPS8L3	ENST00000361965.9	TSL:1 MANE Select	c.1200+96C>A		intron	N/A	ENSP00000355255.4
	EPS8L3	ENST00000369805.7	TSL:1	c.1203+96C>A		intron	N/A	ENSP00000358820.3
	EPS8L3	ENST00000361852.8	TSL:1	c.1200+96C>A		intron	N/A	ENSP00000354551.4

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

African (AFR) AF: 0.557 AC: 12795 AN: 22956

American (AMR) AF: 0.231 AC: 8280 AN: 35848

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 6871 AN: 20606

East Asian (EAS) AF: 0.0938 AC: 3461 AN: 36900

South Asian (SAS) AF: 0.270 AC: 18748 AN: 69394

European-Finnish (FIN) AF: 0.271 AC: 13618 AN: 50204

Middle Eastern (MID) AF: 0.314 AC: 1428 AN: 4546

European-Non Finnish (NFE) AF: 0.295 AC: 200393 AN: 679730

Other (OTH) AF: 0.299 AC: 13042 AN: 43620

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

African (AFR) AF: 0.555 AC: 22994 AN: 41448

American (AMR) AF: 0.280 AC: 4270 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1138 AN: 3472

East Asian (EAS) AF: 0.0863 AC: 447 AN: 5180

South Asian (SAS) AF: 0.269 AC: 1295 AN: 4818

European-Finnish (FIN) AF: 0.283 AC: 2999 AN: 10580

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.302 AC: 20499 AN: 67930

Other (OTH) AF: 0.321 AC: 678 AN: 2112

Alfa AF: 0.315 Hom.: 5965

Bravo AF: 0.367

Asia WGS AF: 0.211 AC: 735 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.9
DANN	Benign	0.91
PhyloP100		1.8
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: rs1887546; hg19: chr1-110295643; COSMIC: COSV62609395; COSMIC: COSV62609395;