rs6694583

Variant names:

• chr1-51498091-G-A
• rs6694583
• NM_001981.3:c.34-16777C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001981.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPS15	NM_001981.3	MANE Select	c.34-16777C>T		intron	N/A	NP_001972.1	P42566-1
	EPS15	NM_001410797.1		c.34-16777C>T		intron	N/A	NP_001397726.1	A0A994J5A3
	EPS15	NM_001410796.1		c.34-16777C>T		intron	N/A	NP_001397725.1	A0A994J5J3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPS15	ENST00000371733.8	TSL:1 MANE Select	c.34-16777C>T		intron	N/A	ENSP00000360798.3	P42566-1
	EPS15	ENST00000371730.6	TSL:1	c.34-16777C>T		intron	N/A	ENSP00000360795.2	B1AUU8
	EPS15	ENST00000706292.1		c.34-16777C>T		intron	N/A	ENSP00000516336.1	A0A994J5A3

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

African (AFR) AF: 0.570 AC: 23585 AN: 41390

American (AMR) AF: 0.193 AC: 2949 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 753 AN: 3458

East Asian (EAS) AF: 0.0111 AC: 57 AN: 5130

South Asian (SAS) AF: 0.110 AC: 531 AN: 4806

European-Finnish (FIN) AF: 0.122 AC: 1275 AN: 10484

Middle Eastern (MID) AF: 0.291 AC: 85 AN: 292

European-Non Finnish (NFE) AF: 0.227 AC: 15431 AN: 67898

Other (OTH) AF: 0.259 AC: 544 AN: 2104

Alfa AF: 0.279 Hom.: 1137

Bravo AF: 0.319

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.60
DANN	Benign	0.60
PhyloP100		-0.79
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: rs6694583; hg19: chr1-51963763;