3-155384042-T-C

Variant names:

• chr3-155384042-T-C
• rs4234306
• ENST00000494598.5:c.2939-8253A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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]

PLCH1 Gene-Disease associations (from GenCC):

• holoprosencephaly 14

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCH1	ENST00000494598.5	c.2939-8253A>G		intron_variant	Intron 21 of 21	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

African (AFR) AF: 0.882 AC: 36621 AN: 41524

American (AMR) AF: 0.619 AC: 9466 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 2073 AN: 3472

East Asian (EAS) AF: 0.492 AC: 2551 AN: 5180

South Asian (SAS) AF: 0.539 AC: 2594 AN: 4812

European-Finnish (FIN) AF: 0.534 AC: 5641 AN: 10562

Middle Eastern (MID) AF: 0.590 AC: 170 AN: 288

European-Non Finnish (NFE) AF: 0.541 AC: 36781 AN: 67966

Other (OTH) AF: 0.599 AC: 1266 AN: 2114

Alfa AF: 0.575 Hom.: 99147

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
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4234306; hg19: chr3-155101831;