3-155548315-T-C

Variant names:

• chr3-155548315-T-C
• rs181696
• NM_014996.4:c.1362+1472A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014996.4(PLCH1):​c.1362+1472A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 152,108 control chromosomes in the GnomAD database, including 27,712 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 0.55 (27712 hom., cov: 32)
• Consequence: PLCH1 NM_014996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430
• Publications: 6 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=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCH1	NM_014996.4	c.1362+1472A>G		intron_variant	Intron 10 of 22	ENST00000460012.7	NP_055811.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCH1	ENST00000460012.7	c.1362+1472A>G		intron_variant	Intron 10 of 22	5	NM_014996.4	ENSP00000417502.2

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83439 AN: 151990 Hom.: 27711 Cov.: 32

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.849

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.758

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.749

Gnomad OTH AF: 0.596

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

GnomAD4 genome AF: 0.549 AC: 83453 AN: 152108 Hom.: 27712 Cov.: 32 AF XY: 0.544 AC XY: 40472 AN XY: 74372

African (AFR) AF: 0.189 AC: 7836 AN: 41508

American (AMR) AF: 0.560 AC: 8542 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2391 AN: 3466

East Asian (EAS) AF: 0.277 AC: 1433 AN: 5170

South Asian (SAS) AF: 0.437 AC: 2107 AN: 4826

European-Finnish (FIN) AF: 0.758 AC: 8017 AN: 10574

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.749 AC: 50891 AN: 67984

Other (OTH) AF: 0.598 AC: 1263 AN: 2112

Alfa AF: 0.633 Hom.: 12735

Bravo AF: 0.522

Asia WGS AF: 0.365 AC: 1272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.2
DANN	Benign	0.76
PhyloP100		0.043
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs181696; hg19: chr3-155266104;