2-198137839-A-T

Position:

• chr2-198137839-A-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCL1	NM_006226.4	c.3106-8941A>T		intron_variant		ENST00000428675.6
PLCL1	XM_005246643.5	c.2884-8941A>T		intron_variant
PLCL1	XM_005246644.5	c.2869-8941A>T		intron_variant
PLCL1	XM_017004339.3	c.2869-8941A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCL1	ENST00000428675.6	c.3106-8941A>T		intron_variant		1	NM_006226.4	P1
PLCL1	ENST00000487695.6	c.2884-8941A>T		intron_variant		5
PLCL1	ENST00000435320.1	c.*2878-8941A>T		intron_variant, NMD_transcript_variant		2

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

Gnomad4 AFR AF: 0.848

Gnomad4 AMR AF: 0.902

Gnomad4 ASJ AF: 0.915

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.956

Gnomad4 FIN AF: 0.880

Gnomad4 NFE AF: 0.888

Gnomad4 OTH AF: 0.896

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.2
DANN	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs10168722; hg19: chr2-199002563;