chr1-109753021-G-T

Position:

• chr1-109753021-G-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.69).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPS8L3	NM_133181.4	c.1200+96C>A		intron_variant		ENST00000361965.9	NP_573444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPS8L3	ENST00000361965.9	c.1200+96C>A		intron_variant		1	NM_133181.4	ENSP00000355255.4

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

Gnomad4 AFR exome AF: 0.557

Gnomad4 AMR exome AF: 0.231

Gnomad4 ASJ exome AF: 0.333

Gnomad4 EAS exome AF: 0.0938

Gnomad4 SAS exome AF: 0.270

Gnomad4 FIN exome AF: 0.271

Gnomad4 NFE exome AF: 0.295

Gnomad4 OTH exome AF: 0.299

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

Gnomad4 AFR AF: 0.555

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.0863

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.321

Alfa AF: 0.317 Hom.: 4300

Bravo AF: 0.367

Asia WGS AF: 0.211 AC: 735 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.9
DANN	Benign	0.91

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

Publications

LitVar

Other links and lift over

dbSNP: rs1887546; hg19: chr1-110295643; COSMIC: COSV62609395; COSMIC: COSV62609395;