rs718712

Variant names:

• chr20-8785361-G-A
• rs718712
• NM_015192.4:c.3112-3088G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-8785361-G-A
• chr20-8785361-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015192.4(PLCB1):​c.3112-3088G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 151,986 control chromosomes in the GnomAD database, including 7,927 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 0.32 (7927 hom., cov: 32)
• Consequence: PLCB1 NM_015192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.714
• Publications: 4 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCB1	NM_015192.4	c.3112-3088G>A		intron_variant	Intron 27 of 31	ENST00000338037.11	NP_056007.1
PLCB1	NM_182734.3	c.3112-3088G>A		intron_variant	Intron 27 of 32		NP_877398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCB1	ENST00000338037.11	c.3112-3088G>A		intron_variant	Intron 27 of 31	1	NM_015192.4	ENSP00000338185.6

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48900 AN: 151866 Hom.: 7918 Cov.: 32

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.322 AC: 48930 AN: 151986 Hom.: 7927 Cov.: 32 AF XY: 0.321 AC XY: 23834 AN XY: 74276

African (AFR) AF: 0.338 AC: 14029 AN: 41452

American (AMR) AF: 0.306 AC: 4669 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1331 AN: 3470

East Asian (EAS) AF: 0.341 AC: 1762 AN: 5162

South Asian (SAS) AF: 0.396 AC: 1904 AN: 4808

European-Finnish (FIN) AF: 0.269 AC: 2836 AN: 10552

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21160 AN: 67958

Other (OTH) AF: 0.357 AC: 751 AN: 2106

Alfa AF: 0.232 Hom.: 760

Bravo AF: 0.321

Asia WGS AF: 0.359 AC: 1245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.8
DANN	Benign	0.82
PhyloP100		0.71
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: rs718712; hg19: chr20-8766008;