20-8723905-T-C

Variant names:

• chr20-8723905-T-C
• rs6077414
• NM_015192.4:c.1582-751T>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.1582-751T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.926 in 151,318 control chromosomes in the GnomAD database, including 65,060 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 0.93 (65060 hom., cov: 26)
• Consequence: PLCB1 NM_015192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85
• Publications: 8 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015192.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCB1	NM_015192.4	MANE Select	c.1582-751T>C		intron	N/A	NP_056007.1
	PLCB1	NM_182734.3		c.1582-751T>C		intron	N/A	NP_877398.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCB1	ENST00000338037.11	TSL:1 MANE Select	c.1582-751T>C		intron	N/A	ENSP00000338185.6
	PLCB1	ENST00000378637.6	TSL:1	c.1582-751T>C		intron	N/A	ENSP00000367904.2
	PLCB1	ENST00000378641.7	TSL:1	c.1582-751T>C		intron	N/A	ENSP00000367908.3

Frequencies

GnomAD3 genomes AF: 0.926 AC: 140073 AN: 151200 Hom.: 65005 Cov.: 26

Gnomad AFR AF: 0.980

Gnomad AMI AF: 0.962

Gnomad AMR AF: 0.890

Gnomad ASJ AF: 0.924

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.927

Gnomad FIN AF: 0.890

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.902

Gnomad OTH AF: 0.927

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

GnomAD4 genome AF: 0.926 AC: 140189 AN: 151318 Hom.: 65060 Cov.: 26 AF XY: 0.928 AC XY: 68553 AN XY: 73894

African (AFR) AF: 0.980 AC: 40470 AN: 41286

American (AMR) AF: 0.890 AC: 13522 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.924 AC: 3201 AN: 3466

East Asian (EAS) AF: 0.999 AC: 5059 AN: 5064

South Asian (SAS) AF: 0.926 AC: 4422 AN: 4774

European-Finnish (FIN) AF: 0.890 AC: 9229 AN: 10372

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.902 AC: 61189 AN: 67860

Other (OTH) AF: 0.927 AC: 1955 AN: 2108

Alfa AF: 0.914 Hom.: 97698

Bravo AF: 0.927

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0040
DANN	Benign	0.41
PhyloP100		-1.9
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: rs6077414; hg19: chr20-8704552;