rs1065754

Positions:

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

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001981.3(EPS15):​c.1329C>T​(p.Tyr443=) 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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPS15	NM_001981.3	c.1329C>T	p.Tyr443=	synonymous_variant	15/25	ENST00000371733.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPS15	ENST00000371733.8	c.1329C>T	p.Tyr443=	synonymous_variant	15/25	1	NM_001981.3	P3

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

GnomAD3 exomes AF: 0.732 AC: 183968 AN: 251432 Hom.: 68921 AF XY: 0.722 AC XY: 98123 AN XY: 135894

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 SAS exome AF: 0.768

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

Gnomad4 AFR exome AF: 0.879

Gnomad4 AMR exome AF: 0.791

Gnomad4 ASJ exome AF: 0.573

Gnomad4 EAS exome AF: 0.990

Gnomad4 SAS exome AF: 0.762

Gnomad4 FIN exome AF: 0.710

Gnomad4 NFE exome AF: 0.659

Gnomad4 OTH exome AF: 0.693

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

Gnomad4 AFR AF: 0.879

Gnomad4 AMR AF: 0.729

Gnomad4 ASJ AF: 0.575

Gnomad4 EAS AF: 0.992

Gnomad4 SAS AF: 0.781

Gnomad4 FIN AF: 0.711

Gnomad4 NFE AF: 0.657

Gnomad4 OTH AF: 0.697

Alfa AF: 0.683 Hom.: 32275

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.29
DANN	Benign	0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1065754; hg19: chr1-51873951;