rs1065754

Variant names:

• chr1-51408279-G-A
• rs1065754
• NM_001981.3:c.1329C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-51408279-G-A
• chr1-51408279-G-C
• chr1-51408279-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001981.3(EPS15):​c.1329C>T​(p.Tyr443Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 1,612,114 control chromosomes in the GnomAD database, including 389,759 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 0.74 (42897 hom., cov: 32)
  • Exomes 𝑓: 0.68 (346862 hom.)
• Consequence: EPS15 NM_001981.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.665
• Publications: 28 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=-0.665 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.97 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.1329C>T	p.Tyr443Tyr	synonymous	Exon 15 of 25	NP_001972.1	P42566-1
	EPS15	NM_001410797.1		c.1440C>T	p.Tyr480Tyr	synonymous	Exon 15 of 25	NP_001397726.1	A0A994J5A3
	EPS15	NM_001410796.1		c.1239C>T	p.Tyr413Tyr	synonymous	Exon 14 of 24	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.1329C>T	p.Tyr443Tyr	synonymous	Exon 15 of 25	ENSP00000360798.3	P42566-1
	EPS15	ENST00000371730.6	TSL:1	c.1275+1256C>T		intron	N/A	ENSP00000360795.2	B1AUU8
	EPS15	ENST00000706292.1		c.1440C>T	p.Tyr480Tyr	synonymous	Exon 15 of 25	ENSP00000516336.1	A0A994J5A3

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112741 AN: 151992 Hom.: 42833 Cov.: 32

Gnomad AFR AF: 0.879

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.992

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.657

Gnomad OTH AF: 0.693

GnomAD2 exomes AF: 0.732 AC: 183968 AN: 251432 AF XY: 0.722

Gnomad AFR exome AF: 0.881

Gnomad AMR exome AF: 0.800

Gnomad ASJ exome AF: 0.569

Gnomad EAS exome AF: 0.993

Gnomad FIN exome AF: 0.708

Gnomad NFE exome AF: 0.659

Gnomad OTH exome AF: 0.681

GnomAD4 exome AF: 0.685 AC: 1000068 AN: 1460004 Hom.: 346862 Cov.: 42 AF XY: 0.686 AC XY: 498371 AN XY: 726452

African (AFR) AF: 0.879 AC: 29417 AN: 33464

American (AMR) AF: 0.791 AC: 35391 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 14956 AN: 26116

East Asian (EAS) AF: 0.990 AC: 39305 AN: 39692

South Asian (SAS) AF: 0.762 AC: 65677 AN: 86236

European-Finnish (FIN) AF: 0.710 AC: 37921 AN: 53414

Middle Eastern (MID) AF: 0.590 AC: 3401 AN: 5768

European-Non Finnish (NFE) AF: 0.659 AC: 732190 AN: 1110242

Other (OTH) AF: 0.693 AC: 41810 AN: 60352

GnomAD4 genome AF: 0.742 AC: 112865 AN: 152110 Hom.: 42897 Cov.: 32 AF XY: 0.748 AC XY: 55587 AN XY: 74318

African (AFR) AF: 0.879 AC: 36490 AN: 41530

American (AMR) AF: 0.729 AC: 11135 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1995 AN: 3470

East Asian (EAS) AF: 0.992 AC: 5140 AN: 5180

South Asian (SAS) AF: 0.781 AC: 3766 AN: 4820

European-Finnish (FIN) AF: 0.711 AC: 7509 AN: 10556

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.657 AC: 44639 AN: 67960

Other (OTH) AF: 0.697 AC: 1470 AN: 2108

Alfa AF: 0.689 Hom.: 41092

Bravo AF: 0.749

Asia WGS AF: 0.893 AC: 3105 AN: 3478

EpiCase AF: 0.641

EpiControl AF: 0.639

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.29
DANN	Benign	0.46
PhyloP100		-0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	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: rs1065754; hg19: chr1-51873951; COSMIC: COSV108207808; COSMIC: COSV108207808;