20-8475677-T-C

Variant names:

• chr20-8475677-T-C
• rs10485724
• NM_015192.4:c.246+104227T>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.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
• 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

LOC124900459 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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.246+104227T>C		intron	N/A	NP_056007.1	Q9NQ66-1
	PLCB1	NM_182734.3		c.246+104227T>C		intron	N/A	NP_877398.1	Q9NQ66-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCB1	ENST00000338037.11	TSL:1 MANE Select	c.246+104227T>C		intron	N/A	ENSP00000338185.6	Q9NQ66-1
	PLCB1	ENST00000378637.6	TSL:1	c.246+104227T>C		intron	N/A	ENSP00000367904.2	Q9NQ66-2
	PLCB1	ENST00000378641.7	TSL:1	c.246+104227T>C		intron	N/A	ENSP00000367908.3	Q9NQ66-2

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

African (AFR) AF: 0.257 AC: 10665 AN: 41454

American (AMR) AF: 0.218 AC: 3327 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1285 AN: 3464

East Asian (EAS) AF: 0.167 AC: 864 AN: 5170

South Asian (SAS) AF: 0.204 AC: 981 AN: 4818

European-Finnish (FIN) AF: 0.241 AC: 2549 AN: 10582

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21217 AN: 67920

Other (OTH) AF: 0.301 AC: 636 AN: 2114

Alfa AF: 0.273 Hom.: 3238

Bravo AF: 0.273

Asia WGS AF: 0.188 AC: 654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.47
DANN	Benign	0.54
PhyloP100		-1.3
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: rs10485724; hg19: chr20-8456324;