rs186797959

chr20-8765121-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS1

The NM_015192.4(PLCB1):c.2711-18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0018 in 1,599,896 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0018 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (5 hom.)
• Consequence: PLCB1 NM_015192.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.115

Genes affected

PLCB1 (HGNC:15917): (phospholipase C beta 1) The protein encoded by this gene catalyzes the formation of inositol 1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate. This reaction uses calcium as a cofactor and plays an important role in the intracellular transduction of many extracellular signals. This gene is activated by two G-protein alpha subunits, alpha-q and alpha-11. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 20-8765121-C-T is Benign according to our data. Variant chr20-8765121-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 260596.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-8765121-C-T is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0018 (274/152254) while in subpopulation NFE AF= 0.00325 (221/68008). AF 95% confidence interval is 0.0029. There are 1 homozygotes in gnomad4. There are 115 alleles in male gnomad4 subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCB1	NM_015192.4	c.2711-18C>T		intron_variant		ENST00000338037.11
PLCB1	NM_182734.3	c.2711-18C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCB1	ENST00000338037.11	c.2711-18C>T		intron_variant		1	NM_015192.4	P1

Frequencies

GnomAD3 genomes AF: 0.00180 AC: 274 AN: 152136 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00325

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00189 AC: 462 AN: 244876 Hom.: 1 AF XY: 0.00196 AC XY: 259 AN XY: 132134

Gnomad AFR exome AF: 0.000125

Gnomad AMR exome AF: 0.00147

Gnomad ASJ exome AF: 0.000414

Gnomad EAS exome AF: 0.0000554

Gnomad SAS exome AF: 0.000734

Gnomad FIN exome AF: 0.00102

Gnomad NFE exome AF: 0.00310

Gnomad OTH exome AF: 0.00286

GnomAD4 exome AF: 0.00179 AC: 2598 AN: 1447642 Hom.: 5 Cov.: 29 AF XY: 0.00189 AC XY: 1363 AN XY: 720376

Gnomad4 AFR exome AF: 0.000518

Gnomad4 AMR exome AF: 0.00138

Gnomad4 ASJ exome AF: 0.000505

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000618

Gnomad4 FIN exome AF: 0.00126

Gnomad4 NFE exome AF: 0.00197

Gnomad4 OTH exome AF: 0.00202

GnomAD4 genome AF: 0.00180 AC: 274 AN: 152254 Hom.: 1 Cov.: 32 AF XY: 0.00154 AC XY: 115 AN XY: 74436

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00325

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00379 Hom.: 0

Bravo AF: 0.00174

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Developmental and epileptic encephalopathy, 12 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 19, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	2.8
Dann	Benign	0.57

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: rs186797959; hg19: chr20-8745768;