19-16437564-A-G

Variant names:

• chr19-16437564-A-G
• rs10411936
• NM_001258374.3:c.309+206T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001258374.3(EPS15L1):​c.309+206T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 152,052 control chromosomes in the GnomAD database, including 31,058 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 0.63 (31058 hom., cov: 32)
• Consequence: EPS15L1 NM_001258374.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.861
• Publications: 29 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPS15L1	NM_001258374.3	c.309+206T>C		intron_variant	Intron 5 of 23	ENST00000455140.7	NP_001245303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPS15L1	ENST00000455140.7	c.309+206T>C		intron_variant	Intron 5 of 23	2	NM_001258374.3	ENSP00000393313.1

Frequencies

GnomAD3 genomes AF: 0.632 AC: 95978 AN: 151934 Hom.: 31057 Cov.: 32

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.767

Gnomad AMR AF: 0.656

Gnomad ASJ AF: 0.813

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.700

Gnomad OTH AF: 0.671

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

GnomAD4 genome AF: 0.631 AC: 96011 AN: 152052 Hom.: 31058 Cov.: 32 AF XY: 0.631 AC XY: 46926 AN XY: 74320

African (AFR) AF: 0.483 AC: 20022 AN: 41450

American (AMR) AF: 0.656 AC: 10019 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.813 AC: 2820 AN: 3470

East Asian (EAS) AF: 0.608 AC: 3147 AN: 5180

South Asian (SAS) AF: 0.742 AC: 3576 AN: 4818

European-Finnish (FIN) AF: 0.614 AC: 6486 AN: 10562

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.700 AC: 47612 AN: 67988

Other (OTH) AF: 0.671 AC: 1417 AN: 2112

Alfa AF: 0.616 Hom.: 18831

Bravo AF: 0.623

Asia WGS AF: 0.642 AC: 2233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.48
DANN	Benign	0.58
PhyloP100		-0.86
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: rs10411936; hg19: chr19-16548375;