20-8788533-C-T

Variant names:

• chr20-8788533-C-T
• rs2327089
• NM_015192.4:c.3188+8C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015192.4(PLCB1):​c.3188+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.952 in 1,611,776 control chromosomes in the GnomAD database, including 731,822 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.90 (62564 hom., cov: 34)
  • Exomes 𝑓: 0.96 (669258 hom.)
• Consequence: PLCB1 NM_015192.4 splice_region, intron
• Scores: Splicing: ADA: 0.00008477
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: 0.0510
• Publications: 13 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 20-8788533-C-T is Benign according to our data. Variant chr20-8788533-C-T is described in ClinVar as Benign. ClinVar VariationId is 129912.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.3188+8C>T		splice_region intron	N/A	NP_056007.1
	PLCB1	NM_182734.3		c.3188+8C>T		splice_region 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.3188+8C>T		splice_region intron	N/A	ENSP00000338185.6
	PLCB1	ENST00000378637.6	TSL:1	c.3188+8C>T		splice_region intron	N/A	ENSP00000367904.2
	PLCB1	ENST00000378641.7	TSL:1	c.3188+8C>T		splice_region intron	N/A	ENSP00000367908.3

Frequencies

GnomAD3 genomes AF: 0.902 AC: 137162 AN: 152142 Hom.: 62540 Cov.: 34

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.947

Gnomad AMR AF: 0.942

Gnomad ASJ AF: 0.918

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.940

Gnomad FIN AF: 0.987

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.962

Gnomad OTH AF: 0.907

GnomAD2 exomes AF: 0.947 AC: 235373 AN: 248588 AF XY: 0.948

Gnomad AFR exome AF: 0.743

Gnomad AMR exome AF: 0.969

Gnomad ASJ exome AF: 0.919

Gnomad EAS exome AF: 0.998

Gnomad FIN exome AF: 0.986

Gnomad NFE exome AF: 0.961

Gnomad OTH exome AF: 0.945

GnomAD4 exome AF: 0.957 AC: 1396571 AN: 1459516 Hom.: 669258 Cov.: 33 AF XY: 0.956 AC XY: 694111 AN XY: 725930

African (AFR) AF: 0.738 AC: 24660 AN: 33408

American (AMR) AF: 0.965 AC: 42997 AN: 44548

Ashkenazi Jewish (ASJ) AF: 0.919 AC: 23972 AN: 26078

East Asian (EAS) AF: 0.999 AC: 39598 AN: 39624

South Asian (SAS) AF: 0.929 AC: 79734 AN: 85800

European-Finnish (FIN) AF: 0.983 AC: 52458 AN: 53358

Middle Eastern (MID) AF: 0.880 AC: 5068 AN: 5760

European-Non Finnish (NFE) AF: 0.965 AC: 1071203 AN: 1110620

Other (OTH) AF: 0.943 AC: 56881 AN: 60320

GnomAD4 genome AF: 0.901 AC: 137239 AN: 152260 Hom.: 62564 Cov.: 34 AF XY: 0.904 AC XY: 67293 AN XY: 74450

African (AFR) AF: 0.746 AC: 30973 AN: 41514

American (AMR) AF: 0.942 AC: 14409 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.918 AC: 3189 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5166 AN: 5172

South Asian (SAS) AF: 0.940 AC: 4533 AN: 4824

European-Finnish (FIN) AF: 0.987 AC: 10481 AN: 10622

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.962 AC: 65436 AN: 68042

Other (OTH) AF: 0.908 AC: 1921 AN: 2116

Alfa AF: 0.926 Hom.: 46473

Bravo AF: 0.892

Asia WGS AF: 0.960 AC: 3339 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Developmental and epileptic encephalopathy, 12 (4)
-	-	4	not specified (4)
-	-	3	not provided (3)
-	-	1	Early Infantile Epileptic Encephalopathy, Autosomal Recessive (1)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.5
DANN	Benign	0.59
PhyloP100		0.051
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000085
dbscSNV1_RF	Benign	0.0
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: rs2327089; hg19: chr20-8769180;