rs11102001

Variant names:

• chr1-109757069-G-A
• rs11102001
• NM_133181.4:c.1066C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-109757069-G-A
• chr1-109757069-G-C

Variant summary

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

The NM_133181.4(EPS8L3):​c.1066C>T​(p.Pro356Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0785 in 1,613,934 control chromosomes in the GnomAD database, including 8,986 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (3233 hom., cov: 32)
  • Exomes 𝑓: 0.071 (5753 hom.)
• Consequence: EPS8L3 NM_133181.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.203
• Publications: 30 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 (MetaRNN=0.002686292).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.364 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.1066C>T	p.Pro356Ser	missense	Exon 12 of 19	NP_573444.2
	EPS8L3	NM_139053.3		c.1069C>T	p.Pro357Ser	missense	Exon 12 of 19	NP_620641.1
	EPS8L3	NM_024526.4		c.1066C>T	p.Pro356Ser	missense	Exon 12 of 19	NP_078802.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPS8L3	ENST00000361965.9	TSL:1 MANE Select	c.1066C>T	p.Pro356Ser	missense	Exon 12 of 19	ENSP00000355255.4
	EPS8L3	ENST00000369805.7	TSL:1	c.1069C>T	p.Pro357Ser	missense	Exon 12 of 19	ENSP00000358820.3
	EPS8L3	ENST00000361852.8	TSL:1	c.1066C>T	p.Pro356Ser	missense	Exon 12 of 19	ENSP00000354551.4

Frequencies

GnomAD3 genomes AF: 0.151 AC: 23009 AN: 152014 Hom.: 3230 Cov.: 32

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.0547

Gnomad EAS AF: 0.00906

Gnomad SAS AF: 0.0756

Gnomad FIN AF: 0.0642

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0610

Gnomad OTH AF: 0.129

GnomAD2 exomes AF: 0.0936 AC: 23531 AN: 251378 AF XY: 0.0858

Gnomad AFR exome AF: 0.377

Gnomad AMR exome AF: 0.161

Gnomad ASJ exome AF: 0.0649

Gnomad EAS exome AF: 0.00179

Gnomad FIN exome AF: 0.0605

Gnomad NFE exome AF: 0.0614

Gnomad OTH exome AF: 0.0755

GnomAD4 exome AF: 0.0709 AC: 103587 AN: 1461802 Hom.: 5753 Cov.: 32 AF XY: 0.0699 AC XY: 50842 AN XY: 727202

African (AFR) AF: 0.379 AC: 12679 AN: 33464

American (AMR) AF: 0.155 AC: 6950 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0636 AC: 1662 AN: 26134

East Asian (EAS) AF: 0.0221 AC: 876 AN: 39700

South Asian (SAS) AF: 0.0805 AC: 6942 AN: 86252

European-Finnish (FIN) AF: 0.0595 AC: 3180 AN: 53418

Middle Eastern (MID) AF: 0.0999 AC: 576 AN: 5768

European-Non Finnish (NFE) AF: 0.0593 AC: 65972 AN: 1111958

Other (OTH) AF: 0.0787 AC: 4750 AN: 60390

GnomAD4 genome AF: 0.151 AC: 23035 AN: 152132 Hom.: 3233 Cov.: 32 AF XY: 0.149 AC XY: 11065 AN XY: 74400

African (AFR) AF: 0.369 AC: 15288 AN: 41456

American (AMR) AF: 0.124 AC: 1895 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0547 AC: 190 AN: 3472

East Asian (EAS) AF: 0.00889 AC: 46 AN: 5174

South Asian (SAS) AF: 0.0759 AC: 366 AN: 4824

European-Finnish (FIN) AF: 0.0642 AC: 681 AN: 10608

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0610 AC: 4150 AN: 67998

Other (OTH) AF: 0.128 AC: 269 AN: 2108

Alfa AF: 0.0863 Hom.: 4859

Bravo AF: 0.165

TwinsUK AF: 0.0599 AC: 222

ALSPAC AF: 0.0576 AC: 222

ESP6500AA AF: 0.365 AC: 1606

ESP6500EA AF: 0.0628 AC: 540

ExAC AF: 0.0980 AC: 11898

Asia WGS AF: 0.0530 AC: 185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.0027	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.20
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Benign	0.091
Sift	Benign	0.067	T
Sift4G	Benign	0.29	T
Polyphen		0.42	B
Vest4		0.14
MPC		0.11
ClinPred		0.015	T
GERP RS		4.5
Varity_R		0.15
gMVP		0.24
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11102001; hg19: chr1-110299691; COSMIC: COSV62609123; COSMIC: COSV62609123;