3-155690413-A-G

Variant summary

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

The NM_014996.4(PLCH1):c.79+13733T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,236 control chromosomes in the GnomAD database, including 2,405 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 0.16 (2405 hom., cov: 32)
• Consequence: PLCH1 NM_014996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.54

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCH1	NM_014996.4	c.79+13733T>C		intron_variant		ENST00000460012.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCH1	ENST00000460012.7	c.79+13733T>C		intron_variant		5	NM_014996.4	P1
PLCH1	ENST00000334686.6	c.-12+13733T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24178 AN: 152118 Hom.: 2405 Cov.: 32

Gnomad AFR AF: 0.0882

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.159 AC: 24187 AN: 152236 Hom.: 2405 Cov.: 32 AF XY: 0.166 AC XY: 12342 AN XY: 74446

Gnomad4 AFR AF: 0.0881

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.144

Alfa AF: 0.120 Hom.: 288

Bravo AF: 0.161

Asia WGS AF: 0.314 AC: 1088 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	10
Dann	Benign	0.47

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: rs358912; hg19: chr3-155408202;