3-155690413-A-G

Variant names:

• chr3-155690413-A-G
• rs358912
• NM_014996.4:c.79+13733T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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 (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCH1	NM_014996.4	c.79+13733T>C		intron_variant	Intron 2 of 22	ENST00000460012.7	NP_055811.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCH1	ENST00000460012.7	c.79+13733T>C		intron_variant	Intron 2 of 22	5	NM_014996.4	ENSP00000417502.2
PLCH1	ENST00000334686.6	c.-12+13733T>C		intron_variant	Intron 1 of 21	1		ENSP00000335469.6

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

African (AFR) AF: 0.0881 AC: 3659 AN: 41554

American (AMR) AF: 0.255 AC: 3897 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 419 AN: 3472

East Asian (EAS) AF: 0.433 AC: 2239 AN: 5170

South Asian (SAS) AF: 0.311 AC: 1495 AN: 4810

European-Finnish (FIN) AF: 0.161 AC: 1709 AN: 10620

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10324 AN: 68014

Other (OTH) AF: 0.144 AC: 304 AN: 2112

Alfa AF: 0.119 Hom.: 291

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
PhyloP100		2.5
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: rs358912; hg19: chr3-155408202;