rs12746918

Positions:

• chr1-2416027-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047435029.1(PLCH2):​c.-178+15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,184 control chromosomes in the GnomAD database, including 3,389 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 0.20 (3389 hom., cov: 33)
• Consequence: PLCH2 XM_047435029.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87

Genes affected

PLCH2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCH2	XM_047435029.1	c.-178+15C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30404 AN: 152066 Hom.: 3381 Cov.: 33

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.0758

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.200 AC: 30435 AN: 152184 Hom.: 3389 Cov.: 33 AF XY: 0.207 AC XY: 15386 AN XY: 74416

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.305

Gnomad4 ASJ AF: 0.0758

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.185

Alfa AF: 0.216 Hom.: 487

Bravo AF: 0.193

Asia WGS AF: 0.202 AC: 703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.84
DANN	Benign	0.53

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12746918; hg19: chr1-2347466;