rs6056188

Positions:

• chr20-8831181-A-G

Variant summary

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

The NM_015192.4(PLCB1):​c.3423+40920A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 152,792 control chromosomes in the GnomAD database, including 19,917 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 0.50 (19831 hom., cov: 32)
  • Exomes 𝑓: 0.40 (86 hom.)
• Consequence: PLCB1 NM_015192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.493

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]

RNU105B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCB1	NM_015192.4	c.3423+40920A>G		intron_variant		ENST00000338037.11	NP_056007.1
PLCB1	NM_182734.3	c.*19+29008A>G		intron_variant			NP_877398.1
RNU105B	NR_004386.2	n.-4A>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCB1	ENST00000338037.11	c.3423+40920A>G		intron_variant		1	NM_015192.4	ENSP00000338185.6

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76533 AN: 151814 Hom.: 19821 Cov.: 32

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.523

GnomAD4 exome AF: 0.400 AC: 344 AN: 860 Hom.: 86 Cov.: 0 AF XY: 0.416 AC XY: 223 AN XY: 536

Gnomad4 AFR exome AF: 0.550

Gnomad4 AMR exome AF: 0.200

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.0750

Gnomad4 SAS exome AF: 0.429

Gnomad4 FIN exome AF: 0.429

Gnomad4 NFE exome AF: 0.409

Gnomad4 OTH exome AF: 0.479

GnomAD4 genome AF: 0.504 AC: 76571 AN: 151932 Hom.: 19831 Cov.: 32 AF XY: 0.501 AC XY: 37171 AN XY: 74232

Gnomad4 AFR AF: 0.594

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.542

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.519

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.487

Gnomad4 OTH AF: 0.524

Alfa AF: 0.486 Hom.: 4353

Bravo AF: 0.499

Asia WGS AF: 0.385 AC: 1343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.5
DANN	Benign	0.61

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: rs6056188; hg19: chr20-8811828;