rs6694583

chr1-51498091-G-A

Variant summary

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

The NM_001981.3(EPS15):c.34-16777C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 151,722 control chromosomes in the GnomAD database, including 9,135 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 0.30 (9135 hom., cov: 32)
• Consequence: EPS15 NM_001981.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.788

Genes affected

EPS15 (HGNC:3419): (epidermal growth factor receptor pathway substrate 15) This gene encodes a protein that is part of the EGFR pathway. The protein is present at clatherin-coated pits and is involved in receptor-mediated endocytosis of EGF. Notably, this gene is rearranged with the HRX/ALL/MLL gene in acute myelogeneous leukemias. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, May 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPS15	NM_001981.3	c.34-16777C>T		intron_variant		ENST00000371733.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPS15	ENST00000371733.8	c.34-16777C>T		intron_variant		1	NM_001981.3	P3

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45376 AN: 151608 Hom.: 9089 Cov.: 32

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.0113

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.300 AC: 45472 AN: 151722 Hom.: 9135 Cov.: 32 AF XY: 0.289 AC XY: 21440 AN XY: 74134

Gnomad4 AFR AF: 0.570

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.0111

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.259

Alfa AF: 0.279 Hom.: 1137

Bravo AF: 0.319

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.60
Dann	Benign	0.60

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: rs6694583; hg19: chr1-51963763;