chr1-51393570-C-T

Variant names:

• chr1-51393570-C-T
• rs6673480
• NM_001981.3:c.2119+811G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001981.3(EPS15):​c.2119+811G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.062 in 152,282 control chromosomes in the GnomAD database, including 313 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 0.062 (313 hom., cov: 32)
• Consequence: EPS15 NM_001981.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 14 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPS15	NM_001981.3	c.2119+811G>A		intron_variant	Intron 21 of 24	ENST00000371733.8	NP_001972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPS15	ENST00000371733.8	c.2119+811G>A		intron_variant	Intron 21 of 24	1	NM_001981.3	ENSP00000360798.3

Frequencies

GnomAD3 genomes AF: 0.0620 AC: 9439 AN: 152164 Hom.: 312 Cov.: 32

Gnomad AFR AF: 0.0598

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.0436

Gnomad ASJ AF: 0.0988

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0263

Gnomad FIN AF: 0.0478

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0745

Gnomad OTH AF: 0.0523

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

GnomAD4 genome AF: 0.0620 AC: 9448 AN: 152282 Hom.: 313 Cov.: 32 AF XY: 0.0600 AC XY: 4468 AN XY: 74462

African (AFR) AF: 0.0599 AC: 2491 AN: 41570

American (AMR) AF: 0.0436 AC: 666 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0988 AC: 343 AN: 3470

East Asian (EAS) AF: 0.000770 AC: 4 AN: 5192

South Asian (SAS) AF: 0.0263 AC: 127 AN: 4830

European-Finnish (FIN) AF: 0.0478 AC: 507 AN: 10604

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0745 AC: 5066 AN: 68012

Other (OTH) AF: 0.0512 AC: 108 AN: 2108

Alfa AF: 0.0702 Hom.: 1297

Bravo AF: 0.0626

Asia WGS AF: 0.0320 AC: 110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.047
DANN	Benign	0.68
PhyloP100		-1.2
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: rs6673480; hg19: chr1-51859242;