chr20-8420020-T-A

Position:

• chr20-8420020-T-A

Variant summary

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

The NM_015192.4(PLCB1):​c.246+48570T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 152,038 control chromosomes in the GnomAD database, including 13,241 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 0.37 (13241 hom., cov: 32)
• Consequence: PLCB1 NM_015192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.278

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCB1	NM_015192.4	c.246+48570T>A		intron_variant		ENST00000338037.11	NP_056007.1
LOC124900459	XR_007067518.1	n.6108-2322T>A		intron_variant, non_coding_transcript_variant
PLCB1	NM_182734.3	c.246+48570T>A		intron_variant			NP_877398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCB1	ENST00000338037.11	c.246+48570T>A		intron_variant		1	NM_015192.4	ENSP00000338185	P1

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55792 AN: 151918 Hom.: 13202 Cov.: 32

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.368 AC: 55891 AN: 152038 Hom.: 13241 Cov.: 32 AF XY: 0.370 AC XY: 27514 AN XY: 74306

Gnomad4 AFR AF: 0.664

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.422

Gnomad4 SAS AF: 0.365

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.318

Alfa AF: 0.150 Hom.: 289

Bravo AF: 0.394

Asia WGS AF: 0.375 AC: 1306 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	9.7
DANN	Benign	0.78

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: rs708915; hg19: chr20-8400667;