rs875622

Variant names:

• chr19-16356948-A-C
• rs875622
• NM_001258374.3:c.2587-1097T>G

Your query was ambiguous. Multiple possible variants found:

• chr19-16356948-A-C
• chr19-16356948-A-G
• chr19-16356948-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001258374.3(EPS15L1):​c.2587-1097T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: EPS15L1 NM_001258374.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.245
• Publications: 0 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

ENSG00000280332 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

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.2587-1097T>G		intron	N/A	NP_001245303.1	Q9UBC2-2
	EPS15L1	NM_001438224.1		c.2635-1097T>G		intron	N/A	NP_001425153.1
	EPS15L1	NM_001438227.1		c.2480-1097T>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.2587-1097T>G		intron	N/A	ENSP00000393313.1	Q9UBC2-2
	EPS15L1	ENST00000602022.5	TSL:1	n.*189-1097T>G		intron	N/A	ENSP00000471981.1	Q9UBC2-3
	EPS15L1	ENST00000945606.1		c.2641-1097T>G		intron	N/A	ENSP00000615665.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.7
DANN	Benign	0.80
PhyloP100		0.24

Splicing

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

Other links and lift over

dbSNP: rs875622; hg19: chr19-16467759;