rs875622

chr19-16356948-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001258374.3(EPS15L1):c.2587-1097T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 151,956 control chromosomes in the GnomAD database, including 37,262 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 0.69 (37248 hom., cov: 31)
  • Exomes 𝑓: 0.74 (14 hom.)
• Consequence: EPS15L1 NM_001258374.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.245

Genes affected

EPS15L1 (HGNC:24634): (epidermal growth factor receptor pathway substrate 15 like 1) Enables cadherin binding activity. Predicted to be involved in endocytosis and endosomal transport. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPS15L1	NM_001258374.3	c.2587-1097T>C		intron_variant		ENST00000455140.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPS15L1	ENST00000455140.7	c.2587-1097T>C		intron_variant		2	NM_001258374.3	P1
	ENST00000623994.1	n.1380T>C		non_coding_transcript_exon_variant	1/1
EPS15L1	ENST00000602022.5	c.*189-1097T>C		intron_variant, NMD_transcript_variant		1
EPS15L1	ENST00000594851.5	c.69-1097T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.691 AC: 104819 AN: 151784 Hom.: 37245 Cov.: 31

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.850

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.873

Gnomad EAS AF: 0.657

Gnomad SAS AF: 0.835

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.744

GnomAD4 exome AF: 0.741 AC: 40 AN: 54 Hom.: 14 Cov.: 0 AF XY: 0.750 AC XY: 21 AN XY: 28

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 0.813

Gnomad4 NFE exome AF: 0.731

Gnomad4 OTH exome AF: 0.700

GnomAD4 genome AF: 0.690 AC: 104850 AN: 151902 Hom.: 37248 Cov.: 31 AF XY: 0.691 AC XY: 51288 AN XY: 74230

Gnomad4 AFR AF: 0.517

Gnomad4 AMR AF: 0.696

Gnomad4 ASJ AF: 0.873

Gnomad4 EAS AF: 0.657

Gnomad4 SAS AF: 0.835

Gnomad4 FIN AF: 0.691

Gnomad4 NFE AF: 0.773

Gnomad4 OTH AF: 0.746

Alfa AF: 0.768 Hom.: 64294

Bravo AF: 0.676

Asia WGS AF: 0.712 AC: 2474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.8
Dann	Benign	0.81

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs875622; hg19: chr19-16467759;