rs3851357

Positions:

• chr3-155549651-G-A
• chr3-155549651-G-T

Variant summary

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

The NM_014996.4(PLCH1):​c.1362+136C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 618,892 control chromosomes in the GnomAD database, including 8,225 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 0.13 (1617 hom., cov: 32)
  • Exomes 𝑓: 0.16 (6608 hom.)
• Consequence: PLCH1 NM_014996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.102

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCH1	NM_014996.4	c.1362+136C>T		intron_variant		ENST00000460012.7	NP_055811.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCH1	ENST00000460012.7	c.1362+136C>T		intron_variant		5	NM_014996.4	ENSP00000417502	P1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19937 AN: 151984 Hom.: 1613 Cov.: 32

Gnomad AFR AF: 0.0443

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.0393

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.122

GnomAD4 exome AF: 0.161 AC: 75272 AN: 466790 Hom.: 6608 AF XY: 0.162 AC XY: 39567 AN XY: 244536

Gnomad4 AFR exome AF: 0.0420

Gnomad4 AMR exome AF: 0.145

Gnomad4 ASJ exome AF: 0.171

Gnomad4 EAS exome AF: 0.0323

Gnomad4 SAS exome AF: 0.147

Gnomad4 FIN exome AF: 0.212

Gnomad4 NFE exome AF: 0.177

Gnomad4 OTH exome AF: 0.159

GnomAD4 genome AF: 0.131 AC: 19943 AN: 152102 Hom.: 1617 Cov.: 32 AF XY: 0.130 AC XY: 9637 AN XY: 74330

Gnomad4 AFR AF: 0.0442

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.0394

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.125

Alfa AF: 0.162 Hom.: 2739

Bravo AF: 0.121

Asia WGS AF: 0.0920 AC: 322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.0
DANN	Benign	0.58

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: rs3851357; hg19: chr3-155267440;