3-155549651-G-A

Variant names:

• chr3-155549651-G-A
• rs3851357
• NM_014996.4:c.1362+136C>T

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+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
• Publications: 8 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014996.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCH1	NM_014996.4	MANE Select	c.1362+136C>T		intron	N/A	NP_055811.2
	PLCH1	NM_001130960.2		c.1326+136C>T		intron	N/A	NP_001124432.1
	PLCH1	NM_001349251.2		c.1362+136C>T		intron	N/A	NP_001336180.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCH1	ENST00000460012.7	TSL:5 MANE Select	c.1362+136C>T		intron	N/A	ENSP00000417502.2
	PLCH1	ENST00000340059.11	TSL:1	c.1326+136C>T		intron	N/A	ENSP00000345988.7
	PLCH1	ENST00000334686.6	TSL:1	c.1272+136C>T		intron	N/A	ENSP00000335469.6

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

African (AFR) AF: 0.0420 AC: 535 AN: 12726

American (AMR) AF: 0.145 AC: 2470 AN: 16988

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 2300 AN: 13414

East Asian (EAS) AF: 0.0323 AC: 995 AN: 30788

South Asian (SAS) AF: 0.147 AC: 6065 AN: 41224

European-Finnish (FIN) AF: 0.212 AC: 6897 AN: 32574

Middle Eastern (MID) AF: 0.125 AC: 243 AN: 1946

European-Non Finnish (NFE) AF: 0.177 AC: 51599 AN: 290896

Other (OTH) AF: 0.159 AC: 4168 AN: 26234

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

African (AFR) AF: 0.0442 AC: 1833 AN: 41494

American (AMR) AF: 0.124 AC: 1892 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 584 AN: 3466

East Asian (EAS) AF: 0.0394 AC: 204 AN: 5174

South Asian (SAS) AF: 0.144 AC: 696 AN: 4826

European-Finnish (FIN) AF: 0.196 AC: 2068 AN: 10552

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12205 AN: 68000

Other (OTH) AF: 0.125 AC: 264 AN: 2112

Alfa AF: 0.157 Hom.: 6048

Bravo AF: 0.121

Asia WGS AF: 0.0920 AC: 322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.0
DANN	Benign	0.58
PhyloP100		-0.10
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: rs3851357; hg19: chr3-155267440;