rs4234306

Positions:

• chr3-155384042-T-C

Variant summary

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

The ENST00000494598.5(PLCH1):​c.2939-8253A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 152,116 control chromosomes in the GnomAD database, including 33,165 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 0.64 (33165 hom., cov: 33)
• Consequence: PLCH1 ENST00000494598.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.199

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.155384042T>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCH1	ENST00000494598.5	c.2939-8253A>G		intron_variant		5		ENSP00000419100.1

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97566 AN: 151998 Hom.: 33100 Cov.: 33

Gnomad AFR AF: 0.882

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.619

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.597

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.598

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

GnomAD4 genome AF: 0.642 AC: 97695 AN: 152116 Hom.: 33165 Cov.: 33 AF XY: 0.639 AC XY: 47474 AN XY: 74344

Gnomad4 AFR AF: 0.882

Gnomad4 AMR AF: 0.619

Gnomad4 ASJ AF: 0.597

Gnomad4 EAS AF: 0.492

Gnomad4 SAS AF: 0.539

Gnomad4 FIN AF: 0.534

Gnomad4 NFE AF: 0.541

Gnomad4 OTH AF: 0.599

Alfa AF: 0.558 Hom.: 42158

Bravo AF: 0.658

Asia WGS AF: 0.572 AC: 1987 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.5
DANN	Benign	0.84

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4234306; hg19: chr3-155101831;