1-51355318-T-G

Variant names:

• chr1-51355318-T-G
• rs7308
• NM_001981.3:c.*1382A>C

Variant summary

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

The NM_001981.3(EPS15):​c.*1382A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 215,614 control chromosomes in the GnomAD database, including 10,948 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 (9139 hom., cov: 32)
  • Exomes 𝑓: 0.21 (1809 hom.)
• Consequence: EPS15 NM_001981.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47
• Publications: 8 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=-0.82).
• 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.*1382A>C		3_prime_UTR	Exon 25 of 25	NP_001972.1	P42566-1
	EPS15	NM_001410797.1		c.*1382A>C		3_prime_UTR	Exon 25 of 25	NP_001397726.1	A0A994J5A3
	EPS15	NM_001410796.1		c.*1382A>C		3_prime_UTR	Exon 24 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.*1382A>C		3_prime_UTR	Exon 25 of 25	ENSP00000360798.3	P42566-1
	EPS15	ENST00000371730.6	TSL:1	c.*1382A>C		3_prime_UTR	Exon 23 of 23	ENSP00000360795.2	B1AUU8
	EPS15	ENST00000706292.1		c.*1382A>C		3_prime_UTR	Exon 25 of 25	ENSP00000516336.1	A0A994J5A3

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45405 AN: 152020 Hom.: 9093 Cov.: 32

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.0111

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.260

GnomAD4 exome AF: 0.208 AC: 13224 AN: 63476 Hom.: 1809 Cov.: 0 AF XY: 0.207 AC XY: 6092 AN XY: 29362

African (AFR) AF: 0.574 AC: 1628 AN: 2834

American (AMR) AF: 0.173 AC: 338 AN: 1956

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 837 AN: 4080

East Asian (EAS) AF: 0.00445 AC: 41 AN: 9206

South Asian (SAS) AF: 0.137 AC: 75 AN: 546

European-Finnish (FIN) AF: 0.148 AC: 13 AN: 88

Middle Eastern (MID) AF: 0.236 AC: 92 AN: 390

European-Non Finnish (NFE) AF: 0.229 AC: 8935 AN: 39084

Other (OTH) AF: 0.239 AC: 1265 AN: 5292

GnomAD4 genome AF: 0.299 AC: 45501 AN: 152138 Hom.: 9139 Cov.: 32 AF XY: 0.288 AC XY: 21454 AN XY: 74388

African (AFR) AF: 0.570 AC: 23643 AN: 41480

American (AMR) AF: 0.193 AC: 2947 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 753 AN: 3470

East Asian (EAS) AF: 0.0110 AC: 57 AN: 5190

South Asian (SAS) AF: 0.110 AC: 531 AN: 4826

European-Finnish (FIN) AF: 0.120 AC: 1274 AN: 10602

Middle Eastern (MID) AF: 0.284 AC: 83 AN: 292

European-Non Finnish (NFE) AF: 0.227 AC: 15406 AN: 67970

Other (OTH) AF: 0.258 AC: 545 AN: 2116

Alfa AF: 0.214 Hom.: 1604

Bravo AF: 0.319

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.9
DANN	Benign	0.69
PhyloP100		1.5
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: rs7308; hg19: chr1-51820990;