20-8475677-T-C

Position:

• chr20-8475677-T-C

Variant summary

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

The NM_015192.4(PLCB1):​c.246+104227T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 151,996 control chromosomes in the GnomAD database, including 6,022 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 0.27 (6022 hom., cov: 32)
• Consequence: PLCB1 NM_015192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

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]

LOC124900459 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCB1	NM_015192.4	c.246+104227T>C		intron_variant		ENST00000338037.11	NP_056007.1
LOC124900459	XR_007067518.1	n.59443T>C		non_coding_transcript_exon_variant	2/2
PLCB1	NM_182734.3	c.246+104227T>C		intron_variant			NP_877398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCB1	ENST00000338037.11	c.246+104227T>C		intron_variant		1	NM_015192.4	ENSP00000338185	P1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41756 AN: 151878 Hom.: 6021 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.275 AC: 41774 AN: 151996 Hom.: 6022 Cov.: 32 AF XY: 0.266 AC XY: 19781 AN XY: 74294

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.301

Alfa AF: 0.268 Hom.: 2831

Bravo AF: 0.273

Asia WGS AF: 0.188 AC: 654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.47
DANN	Benign	0.54

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: rs10485724; hg19: chr20-8456324;