3-155522825-G-T

Variant names:

• chr3-155522825-G-T
• rs10513477
• NM_014996.4:c.1470+1072C>A

Variant summary

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

The NM_014996.4(PLCH1):​c.1470+1072C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0938 in 151,598 control chromosomes in the GnomAD database, including 1,580 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 0.094 (1580 hom., cov: 29)
• Consequence: PLCH1 NM_014996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.138
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.268 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.1470+1072C>A		intron	N/A	NP_055811.2
	PLCH1	NM_001130960.2		c.1434+1072C>A		intron	N/A	NP_001124432.1
	PLCH1	NM_001349251.2		c.1470+1072C>A		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.1470+1072C>A		intron	N/A	ENSP00000417502.2
	PLCH1	ENST00000340059.11	TSL:1	c.1434+1072C>A		intron	N/A	ENSP00000345988.7
	PLCH1	ENST00000334686.6	TSL:1	c.1380+1072C>A		intron	N/A	ENSP00000335469.6

Frequencies

GnomAD3 genomes AF: 0.0937 AC: 14191 AN: 151480 Hom.: 1576 Cov.: 29

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0452

Gnomad ASJ AF: 0.0380

Gnomad EAS AF: 0.00309

Gnomad SAS AF: 0.0319

Gnomad FIN AF: 0.00470

Gnomad MID AF: 0.0382

Gnomad NFE AF: 0.0261

Gnomad OTH AF: 0.0736

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

GnomAD4 genome AF: 0.0938 AC: 14216 AN: 151598 Hom.: 1580 Cov.: 29 AF XY: 0.0909 AC XY: 6733 AN XY: 74046

African (AFR) AF: 0.272 AC: 11242 AN: 41256

American (AMR) AF: 0.0451 AC: 686 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.0380 AC: 132 AN: 3472

East Asian (EAS) AF: 0.00310 AC: 16 AN: 5158

South Asian (SAS) AF: 0.0315 AC: 151 AN: 4798

European-Finnish (FIN) AF: 0.00470 AC: 49 AN: 10420

Middle Eastern (MID) AF: 0.0308 AC: 9 AN: 292

European-Non Finnish (NFE) AF: 0.0261 AC: 1777 AN: 67966

Other (OTH) AF: 0.0723 AC: 152 AN: 2102

Alfa AF: 0.0426 Hom.: 140

Bravo AF: 0.103

Asia WGS AF: 0.0290 AC: 101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.60
PhyloP100		-0.14
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: rs10513477; hg19: chr3-155240614;