3-155620480-A-G

Variant names:

• chr3-155620480-A-G
• rs3908141
• NM_014996.4:c.80-24102T>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.80-24102T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 152,094 control chromosomes in the GnomAD database, including 20,345 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 0.49 (20345 hom., cov: 32)
• Consequence: PLCH1 NM_014996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 4 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.73 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.80-24102T>C		intron	N/A	NP_055811.2
	PLCH1	NM_001130960.2		c.44-24102T>C		intron	N/A	NP_001124432.1
	PLCH1	NM_001349251.2		c.80-24102T>C		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.80-24102T>C		intron	N/A	ENSP00000417502.2
	PLCH1	ENST00000340059.11	TSL:1	c.44-24102T>C		intron	N/A	ENSP00000345988.7
	PLCH1	ENST00000334686.6	TSL:1	c.-11-24102T>C		intron	N/A	ENSP00000335469.6

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73790 AN: 151976 Hom.: 20299 Cov.: 32

Gnomad AFR AF: 0.736

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.435

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

GnomAD4 genome AF: 0.486 AC: 73893 AN: 152094 Hom.: 20345 Cov.: 32 AF XY: 0.491 AC XY: 36484 AN XY: 74348

African (AFR) AF: 0.737 AC: 30572 AN: 41486

American (AMR) AF: 0.467 AC: 7135 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1217 AN: 3470

East Asian (EAS) AF: 0.694 AC: 3585 AN: 5168

South Asian (SAS) AF: 0.628 AC: 3030 AN: 4822

European-Finnish (FIN) AF: 0.362 AC: 3823 AN: 10570

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23228 AN: 67974

Other (OTH) AF: 0.432 AC: 914 AN: 2114

Alfa AF: 0.388 Hom.: 53021

Bravo AF: 0.499

Asia WGS AF: 0.631 AC: 2191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.47
DANN	Benign	0.63
PhyloP100		-1.3
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: rs3908141; hg19: chr3-155338269;