rs700675

Variant names:

• chr2-197835492-G-A
• rs700675
• NM_006226.4:c.240+30153G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-197835492-G-A
• chr2-197835492-G-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+30153G>A 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 152,064 control chromosomes in the GnomAD database, including 41,397 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 (41397 hom., cov: 31)
• Consequence: PLCL1 NM_006226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCL1	NM_006226.4	c.240+30153G>A		intron_variant	Intron 1 of 5	ENST00000428675.6	NP_006217.3
PLCL1	XM_005246643.5	c.18+25170G>A		intron_variant	Intron 1 of 5		XP_005246700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCL1	ENST00000428675.6	c.240+30153G>A		intron_variant	Intron 1 of 5	1	NM_006226.4	ENSP00000402861.1
PLCL1	ENST00000487695.6	c.18+25170G>A		intron_variant	Intron 1 of 5	5		ENSP00000457588.1
PLCL1	ENST00000435320.1	n.240+30153G>A		intron_variant	Intron 1 of 6	2		ENSP00000410488.1
ENSG00000286020	ENST00000650958.2	n.169+703C>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110630 AN: 151946 Hom.: 41346 Cov.: 31

Gnomad AFR AF: 0.905

Gnomad AMI AF: 0.710

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.742

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

GnomAD4 genome AF: 0.728 AC: 110736 AN: 152064 Hom.: 41397 Cov.: 31 AF XY: 0.725 AC XY: 53896 AN XY: 74328

African (AFR) AF: 0.905 AC: 37562 AN: 41514

American (AMR) AF: 0.653 AC: 9987 AN: 15294

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

East Asian (EAS) AF: 0.501 AC: 2583 AN: 5152

South Asian (SAS) AF: 0.656 AC: 3159 AN: 4812

European-Finnish (FIN) AF: 0.608 AC: 6400 AN: 10526

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

European-Non Finnish (NFE) AF: 0.677 AC: 46044 AN: 67982

Other (OTH) AF: 0.742 AC: 1566 AN: 2110

Alfa AF: 0.690 Hom.: 18633

Bravo AF: 0.739

Asia WGS AF: 0.596 AC: 2075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.022
DANN	Benign	0.40
PhyloP100		-2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs700675; hg19: chr2-198700216;