chr2-197822560-T-C

Variant names:

• chr2-197822560-T-C
• rs700670
• NM_006226.4:c.240+17221T>C

Variant summary

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

The NM_006226.4(PLCL1):​c.240+17221T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 152,096 control chromosomes in the GnomAD database, including 41,394 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 0.73 (41394 hom., cov: 33)
• Consequence: PLCL1 NM_006226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• Publications: 8 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]

ENSG00000286020 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006226.4. 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
	PLCL1	NM_006226.4	MANE Select	c.240+17221T>C		intron	N/A	NP_006217.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCL1	ENST00000428675.6	TSL:1 MANE Select	c.240+17221T>C		intron	N/A	ENSP00000402861.1
	PLCL1	ENST00000487695.6	TSL:5	c.18+12238T>C		intron	N/A	ENSP00000457588.1
	PLCL1	ENST00000435320.1	TSL:2	n.240+17221T>C		intron	N/A	ENSP00000410488.1

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110620 AN: 151978 Hom.: 41346 Cov.: 33

Gnomad AFR AF: 0.904

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.743

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

GnomAD4 genome AF: 0.728 AC: 110723 AN: 152096 Hom.: 41394 Cov.: 33 AF XY: 0.725 AC XY: 53896 AN XY: 74362

African (AFR) AF: 0.904 AC: 37582 AN: 41560

American (AMR) AF: 0.653 AC: 9977 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.732 AC: 2540 AN: 3472

East Asian (EAS) AF: 0.501 AC: 2579 AN: 5152

South Asian (SAS) AF: 0.656 AC: 3160 AN: 4816

European-Finnish (FIN) AF: 0.607 AC: 6407 AN: 10562

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.677 AC: 46013 AN: 67940

Other (OTH) AF: 0.742 AC: 1568 AN: 2112

Alfa AF: 0.699 Hom.: 19876

Bravo AF: 0.738

Asia WGS AF: 0.595 AC: 2072 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.26
DANN	Benign	0.44
PhyloP100		-1.8
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: rs700670; hg19: chr2-198687284; COSMIC: COSV70828725;