chr2-198184384-A-G

Variant names:

• chr2-198184384-A-G
• rs6434957
• ENST00000625084.1:n.44+34966A>G

Variant summary

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

The ENST00000625084.1(PLCL1):​n.44+34966A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 152,154 control chromosomes in the GnomAD database, including 10,674 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 0.36 (10674 hom., cov: 33)
• Consequence: PLCL1 ENST00000625084.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.166
• Publications: 1 publications found

Genes affected

PLCL1 (HGNC:9063): (phospholipase C like 1 (inactive)) Predicted to enable phospholipase C activity. Predicted to be involved in negative regulation of cold-induced thermogenesis and phosphatidylinositol-mediated signaling. Predicted to act upstream of or within several processes, including gamma-aminobutyric acid signaling pathway; regulation of GABAergic synaptic transmission; and regulation of peptidyl-serine phosphorylation. Predicted to be located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCL1	ENST00000625084.1	n.44+34966A>G		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54866 AN: 152036 Hom.: 10680 Cov.: 33

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.407

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

GnomAD4 genome AF: 0.361 AC: 54867 AN: 152154 Hom.: 10674 Cov.: 33 AF XY: 0.358 AC XY: 26661 AN XY: 74392

African (AFR) AF: 0.204 AC: 8485 AN: 41534

American (AMR) AF: 0.344 AC: 5259 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 1927 AN: 3468

East Asian (EAS) AF: 0.450 AC: 2331 AN: 5178

South Asian (SAS) AF: 0.346 AC: 1669 AN: 4824

European-Finnish (FIN) AF: 0.400 AC: 4224 AN: 10568

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.435 AC: 29575 AN: 67974

Other (OTH) AF: 0.407 AC: 861 AN: 2114

Alfa AF: 0.418 Hom.: 17680

Bravo AF: 0.353

Asia WGS AF: 0.365 AC: 1269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.80
DANN	Benign	0.76
PhyloP100		-0.17

Splicing

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

Other links and lift over

dbSNP: rs6434957; hg19: chr2-199049108;