rs10513478

Variant names:

• chr3-155522876-C-T
• rs10513478
• NM_014996.4:c.1470+1021G>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+1021G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0671 in 149,860 control chromosomes in the GnomAD database, including 454 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 0.067 (454 hom., cov: 27)
• Consequence: PLCH1 NM_014996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.310
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCH1	NM_014996.4	c.1470+1021G>A		intron_variant	Intron 11 of 22	ENST00000460012.7	NP_055811.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCH1	ENST00000460012.7	c.1470+1021G>A		intron_variant	Intron 11 of 22	5	NM_014996.4	ENSP00000417502.2

Frequencies

GnomAD3 genomes AF: 0.0672 AC: 10056 AN: 149754 Hom.: 453 Cov.: 27

Gnomad AFR AF: 0.0157

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.0745

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.00803

Gnomad SAS AF: 0.0872

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0894

Gnomad OTH AF: 0.0748

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

GnomAD4 genome AF: 0.0671 AC: 10054 AN: 149860 Hom.: 454 Cov.: 27 AF XY: 0.0681 AC XY: 4966 AN XY: 72966

African (AFR) AF: 0.0156 AC: 633 AN: 40530

American (AMR) AF: 0.0744 AC: 1100 AN: 14784

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 523 AN: 3458

East Asian (EAS) AF: 0.00805 AC: 41 AN: 5096

South Asian (SAS) AF: 0.0880 AC: 421 AN: 4786

European-Finnish (FIN) AF: 0.100 AC: 1008 AN: 10076

Middle Eastern (MID) AF: 0.105 AC: 30 AN: 286

European-Non Finnish (NFE) AF: 0.0894 AC: 6066 AN: 67854

Other (OTH) AF: 0.0736 AC: 153 AN: 2078

Alfa AF: 0.0861 Hom.: 982

Bravo AF: 0.0607

Asia WGS AF: 0.0610 AC: 213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.0
DANN	Benign	0.37
PhyloP100		-0.31
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: rs10513478; hg19: chr3-155240665;