rs10513478

Positions:

• chr3-155522876-C-T

Variant summary

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

The NM_014996.4(PLCH1):​c.1470+1021G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0671 in 149,860 control chromosomes in the GnomAD database, including 454 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 0.067 (454 hom., cov: 27)
• Consequence: PLCH1 NM_014996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.310

Genes affected

PLCH1 (HGNC:29185): (phospholipase C eta 1) PLCH1 is a member of the PLC-eta family of the phosphoinositide-specific phospholipase C (PLC) superfamily of enzymes that cleave phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) to generate second messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) (Hwang et al., 2005 [PubMed 15702972]).[supplied by OMIM, Jun 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCH1	NM_014996.4	c.1470+1021G>A		intron_variant		ENST00000460012.7	NP_055811.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCH1	ENST00000460012.7	c.1470+1021G>A		intron_variant		5	NM_014996.4	ENSP00000417502	P1

Frequencies

GnomAD3 genomes AF: 0.0672 AC: 10056 AN: 149754 Hom.: 453 Cov.: 27

Gnomad AFR AF: 0.0157

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.0745

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.00803

Gnomad SAS AF: 0.0872

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0894

Gnomad OTH AF: 0.0748

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

GnomAD4 genome AF: 0.0671 AC: 10054 AN: 149860 Hom.: 454 Cov.: 27 AF XY: 0.0681 AC XY: 4966 AN XY: 72966

Gnomad4 AFR AF: 0.0156

Gnomad4 AMR AF: 0.0744

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.00805

Gnomad4 SAS AF: 0.0880

Gnomad4 FIN AF: 0.100

Gnomad4 NFE AF: 0.0894

Gnomad4 OTH AF: 0.0736

Alfa AF: 0.0899 Hom.: 806

Bravo AF: 0.0607

Asia WGS AF: 0.0610 AC: 213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.0
DANN	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs10513478; hg19: chr3-155240665;