rs708915

Variant names:

• chr20-8420020-T-A
• rs708915
• NM_015192.4:c.246+48570T>A

Your query was ambiguous. Multiple possible variants found:

• chr20-8420020-T-A
• chr20-8420020-T-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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]

PLCB1 Gene-Disease associations (from GenCC):

• genetic developmental and epileptic encephalopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• developmental and epileptic encephalopathy, 12

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• infantile spasms

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• malignant migrating partial seizures of infancy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

LOC124900459 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PLCB1	NM_015192.4	c.246+48570T>A		intron_variant	Intron 3 of 31	ENST00000338037.11	NP_056007.1
PLCB1	NM_182734.3	c.246+48570T>A		intron_variant	Intron 3 of 32		NP_877398.1
LOC124900459	XR_007067518.1	n.6108-2322T>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCB1	ENST00000338037.11	c.246+48570T>A		intron_variant	Intron 3 of 31	1	NM_015192.4	ENSP00000338185.6

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

African (AFR) AF: 0.664 AC: 27524 AN: 41470

American (AMR) AF: 0.390 AC: 5959 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 772 AN: 3470

East Asian (EAS) AF: 0.422 AC: 2184 AN: 5176

South Asian (SAS) AF: 0.365 AC: 1760 AN: 4828

European-Finnish (FIN) AF: 0.246 AC: 2596 AN: 10572

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14275 AN: 67944

Other (OTH) AF: 0.318 AC: 672 AN: 2110

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
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs708915; hg19: chr20-8400667;