rs7595412

Positions:

• chr2-198097519-G-A
• chr2-198097519-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006226.4(PLCL1):​c.2920-3766G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.916 in 152,260 control chromosomes in the GnomAD database, including 63,934 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 0.92 (63934 hom., cov: 32)
• Consequence: PLCL1 NM_006226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194

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=-0.91).
• 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	Protein	UniProt
PLCL1	NM_006226.4	c.2920-3766G>A		intron_variant		ENST00000428675.6	NP_006217.3
PLCL1	XM_005246643.5	c.2698-3766G>A		intron_variant			XP_005246700.1
PLCL1	XM_005246644.5	c.2683-3766G>A		intron_variant			XP_005246701.1
PLCL1	XM_017004339.3	c.2683-3766G>A		intron_variant			XP_016859828.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCL1	ENST00000428675.6	c.2920-3766G>A		intron_variant		1	NM_006226.4	ENSP00000402861	P1
PLCL1	ENST00000487695.6	c.2698-3766G>A		intron_variant		5		ENSP00000457588
PLCL1	ENST00000435320.1	c.*2692-3766G>A		intron_variant, NMD_transcript_variant		2		ENSP00000410488

Frequencies

GnomAD3 genomes AF: 0.916 AC: 139365 AN: 152142 Hom.: 63886 Cov.: 32

Gnomad AFR AF: 0.944

Gnomad AMI AF: 0.872

Gnomad AMR AF: 0.920

Gnomad ASJ AF: 0.915

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.958

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.895

Gnomad OTH AF: 0.919

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

GnomAD4 genome AF: 0.916 AC: 139471 AN: 152260 Hom.: 63934 Cov.: 32 AF XY: 0.917 AC XY: 68227 AN XY: 74422

Gnomad4 AFR AF: 0.944

Gnomad4 AMR AF: 0.920

Gnomad4 ASJ AF: 0.915

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.957

Gnomad4 FIN AF: 0.881

Gnomad4 NFE AF: 0.895

Gnomad4 OTH AF: 0.920

Alfa AF: 0.906 Hom.: 132824

Bravo AF: 0.920

Asia WGS AF: 0.975 AC: 3389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.66

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: rs7595412; hg19: chr2-198962243;