2-198137839-A-T

Variant names:

• chr2-198137839-A-T
• rs10168722
• NM_006226.4:c.3106-8941A>T

Variant summary

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

The NM_006226.4(PLCL1):​c.3106-8941A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.885 in 151,864 control chromosomes in the GnomAD database, including 59,535 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 0.88 (59535 hom., cov: 31)
• Consequence: PLCL1 NM_006226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.206
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 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.3106-8941A>T		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.3106-8941A>T		intron	N/A	ENSP00000402861.1
	PLCL1	ENST00000487695.6	TSL:5	c.2884-8941A>T		intron	N/A	ENSP00000457588.1
	PLCL1	ENST00000435320.1	TSL:2	n.*2878-8941A>T		intron	N/A	ENSP00000410488.1

Frequencies

GnomAD3 genomes AF: 0.885 AC: 134278 AN: 151746 Hom.: 59502 Cov.: 31

Gnomad AFR AF: 0.848

Gnomad AMI AF: 0.871

Gnomad AMR AF: 0.902

Gnomad ASJ AF: 0.915

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.956

Gnomad FIN AF: 0.880

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.888

Gnomad OTH AF: 0.895

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

GnomAD4 genome AF: 0.885 AC: 134362 AN: 151864 Hom.: 59535 Cov.: 31 AF XY: 0.887 AC XY: 65858 AN XY: 74222

African (AFR) AF: 0.848 AC: 35096 AN: 41392

American (AMR) AF: 0.902 AC: 13749 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.915 AC: 3176 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5153 AN: 5160

South Asian (SAS) AF: 0.956 AC: 4606 AN: 4820

European-Finnish (FIN) AF: 0.880 AC: 9291 AN: 10554

Middle Eastern (MID) AF: 0.952 AC: 280 AN: 294

European-Non Finnish (NFE) AF: 0.888 AC: 60339 AN: 67922

Other (OTH) AF: 0.896 AC: 1879 AN: 2098

Alfa AF: 0.858 Hom.: 3000

Bravo AF: 0.885

Asia WGS AF: 0.969 AC: 3367 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.2
DANN	Benign	0.41
PhyloP100		-0.21
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: rs10168722; hg19: chr2-199002563;