rs11878602

Variant names:

• chr19-16444342-A-C
• rs11878602
• NM_001258374.3:c.34-2123T>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.34-2123T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 151,928 control chromosomes in the GnomAD database, including 15,783 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 0.42 (15783 hom., cov: 31)
• Consequence: EPS15L1 NM_001258374.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07
• Publications: 8 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.687 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPS15L1	NM_001258374.3	MANE Select	c.34-2123T>G		intron	N/A	NP_001245303.1
	EPS15L1	NM_001438224.1		c.34-2123T>G		intron	N/A	NP_001425153.1
	EPS15L1	NM_021235.3		c.34-2123T>G		intron	N/A	NP_067058.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPS15L1	ENST00000455140.7	TSL:2 MANE Select	c.34-2123T>G		intron	N/A	ENSP00000393313.1
	EPS15L1	ENST00000248070.10	TSL:1	c.34-2123T>G		intron	N/A	ENSP00000248070.5
	EPS15L1	ENST00000535753.6	TSL:1	c.34-2123T>G		intron	N/A	ENSP00000440103.1

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63762 AN: 151810 Hom.: 15732 Cov.: 31

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.420 AC: 63877 AN: 151928 Hom.: 15783 Cov.: 31 AF XY: 0.419 AC XY: 31144 AN XY: 74268

African (AFR) AF: 0.694 AC: 28731 AN: 41414

American (AMR) AF: 0.365 AC: 5576 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 667 AN: 3466

East Asian (EAS) AF: 0.394 AC: 2035 AN: 5162

South Asian (SAS) AF: 0.260 AC: 1252 AN: 4820

European-Finnish (FIN) AF: 0.387 AC: 4088 AN: 10550

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.301 AC: 20451 AN: 67932

Other (OTH) AF: 0.367 AC: 773 AN: 2108

Alfa AF: 0.322 Hom.: 5353

Bravo AF: 0.437

Asia WGS AF: 0.369 AC: 1283 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.33
DANN	Benign	0.38
PhyloP100		-2.1
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: rs11878602; hg19: chr19-16555153;