chr19-16361060-G-C

Position:

• chr19-16361060-G-C

Variant summary

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

The NM_001258374.3(EPS15L1):​c.2586+719C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 151,966 control chromosomes in the GnomAD database, including 25,249 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 0.55 (25249 hom., cov: 31)
• Consequence: EPS15L1 NM_001258374.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.387

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]

EPS15L1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPS15L1	NM_001258374.3	c.2586+719C>G		intron_variant		ENST00000455140.7	NP_001245303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPS15L1	ENST00000455140.7	c.2586+719C>G		intron_variant		2	NM_001258374.3	ENSP00000393313.1
EPS15L1	ENST00000602022.5	n.*188+719C>G		intron_variant		1		ENSP00000471981.1
EPS15L1	ENST00000594851.5	c.66+826C>G		intron_variant		3		ENSP00000469495.1

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83190 AN: 151846 Hom.: 25250 Cov.: 31

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.619

Gnomad ASJ AF: 0.797

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.604

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

GnomAD4 genome AF: 0.547 AC: 83199 AN: 151966 Hom.: 25249 Cov.: 31 AF XY: 0.550 AC XY: 40831 AN XY: 74262

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.619

Gnomad4 ASJ AF: 0.797

Gnomad4 EAS AF: 0.612

Gnomad4 SAS AF: 0.710

Gnomad4 FIN AF: 0.588

Gnomad4 NFE AF: 0.665

Gnomad4 OTH AF: 0.606

Alfa AF: 0.599 Hom.: 3577

Bravo AF: 0.532

Asia WGS AF: 0.610 AC: 2121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.39
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8113386; hg19: chr19-16471871;