rs2274536

Positions:

• chr1-109751955-A-G

Variant summary

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

The NM_133181.4(EPS8L3):​c.1434+40T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 1,565,574 control chromosomes in the GnomAD database, including 79,918 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 0.38 (12615 hom., cov: 31)
  • Exomes 𝑓: 0.30 (67303 hom.)
• Consequence: EPS8L3 NM_133181.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.368

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPS8L3	NM_133181.4	c.1434+40T>C		intron_variant		ENST00000361965.9	NP_573444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPS8L3	ENST00000361965.9	c.1434+40T>C		intron_variant		1	NM_133181.4	ENSP00000355255.4

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57399 AN: 151740 Hom.: 12586 Cov.: 31

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.483

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.333

GnomAD3 exomes AF: 0.296 AC: 63577 AN: 214480 Hom.: 10811 AF XY: 0.291 AC XY: 33184 AN XY: 113902

Gnomad AFR exome AF: 0.619

Gnomad AMR exome AF: 0.222

Gnomad ASJ exome AF: 0.321

Gnomad EAS exome AF: 0.102

Gnomad SAS exome AF: 0.301

Gnomad FIN exome AF: 0.278

Gnomad NFE exome AF: 0.304

Gnomad OTH exome AF: 0.285

GnomAD4 exome AF: 0.301 AC: 425811 AN: 1413716 Hom.: 67303 Cov.: 32 AF XY: 0.300 AC XY: 209501 AN XY: 697630

Gnomad4 AFR exome AF: 0.617

Gnomad4 AMR exome AF: 0.231

Gnomad4 ASJ exome AF: 0.334

Gnomad4 EAS exome AF: 0.116

Gnomad4 SAS exome AF: 0.295

Gnomad4 FIN exome AF: 0.273

Gnomad4 NFE exome AF: 0.302

Gnomad4 OTH exome AF: 0.309

GnomAD4 genome AF: 0.378 AC: 57478 AN: 151858 Hom.: 12615 Cov.: 31 AF XY: 0.372 AC XY: 27636 AN XY: 74232

Gnomad4 AFR AF: 0.608

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.332

Alfa AF: 0.310 Hom.: 10662

Bravo AF: 0.386

Asia WGS AF: 0.227 AC: 791 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.2
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2274536; hg19: chr1-110294577; COSMIC: COSV62610112; COSMIC: COSV62610112;