19-16361060-G-C

Variant names:

• chr19-16361060-G-C
• rs8113386
• NM_001258374.3:c.2586+719C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• split hand-foot malformation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001258374.3. 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
	EPS15L1	NM_001258374.3	MANE Select	c.2586+719C>G		intron	N/A	NP_001245303.1	Q9UBC2-2
	EPS15L1	NM_001438224.1		c.2634+719C>G		intron	N/A	NP_001425153.1
	EPS15L1	NM_001438227.1		c.2479+826C>G		intron	N/A	NP_001425156.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPS15L1	ENST00000455140.7	TSL:2 MANE Select	c.2586+719C>G		intron	N/A	ENSP00000393313.1	Q9UBC2-2
	EPS15L1	ENST00000602022.5	TSL:1	n.*188+719C>G		intron	N/A	ENSP00000471981.1	Q9UBC2-3
	EPS15L1	ENST00000945606.1		c.2640+719C>G		intron	N/A	ENSP00000615665.1

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

African (AFR) AF: 0.263 AC: 10888 AN: 41398

American (AMR) AF: 0.619 AC: 9443 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.797 AC: 2761 AN: 3464

East Asian (EAS) AF: 0.612 AC: 3169 AN: 5180

South Asian (SAS) AF: 0.710 AC: 3424 AN: 4820

European-Finnish (FIN) AF: 0.588 AC: 6199 AN: 10540

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.665 AC: 45191 AN: 67988

Other (OTH) AF: 0.606 AC: 1277 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.39
DANN	Benign	0.49
PhyloP100		0.39
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs8113386; hg19: chr19-16471871;