20-8132322-C-T

Variant names:

• chr20-8132322-C-T
• rs532302075
• NM_015192.4:c.-330C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6 BS1 BS2

The NM_015192.4(PLCB1):​c.-330C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0066 in 207,664 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0065 (12 hom., cov: 32)
  • Exomes 𝑓: 0.0069 (1 hom.)
• Consequence: PLCB1 NM_015192.4 5_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: 2.70
• Publications: 0 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BP6: Variant 20-8132322-C-T is Benign according to our data. Variant chr20-8132322-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 897290.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00648 (986/152212) while in subpopulation NFE AF = 0.00984 (669/67978). AF 95% confidence interval is 0.00922. There are 12 homozygotes in GnomAd4. There are 506 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 AD,AR gene

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.-330C>T		5_prime_UTR	Exon 1 of 32	NP_056007.1	Q9NQ66-1
	PLCB1	NM_182734.3		c.-330C>T		5_prime_UTR	Exon 1 of 33	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.-330C>T		5_prime_UTR	Exon 1 of 32	ENSP00000338185.6	Q9NQ66-1
	PLCB1	ENST00000378641.7	TSL:1	c.-330C>T		5_prime_UTR	Exon 1 of 33	ENSP00000367908.3	Q9NQ66-2
	PLCB1	ENST00000629992.2	TSL:1	c.-330C>T		5_prime_UTR	Exon 1 of 8	ENSP00000486531.1	A0A0D9SFE7

Frequencies

GnomAD3 genomes AF: 0.00648 AC: 986 AN: 152104 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.00128

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00222

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.0202

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00984

Gnomad OTH AF: 0.00382

GnomAD4 exome AF: 0.00692 AC: 384 AN: 55452 Hom.: 1 Cov.: 0 AF XY: 0.00738 AC XY: 211 AN XY: 28588

African (AFR) AF: 0.000578 AC: 1 AN: 1730

American (AMR) AF: 0.000690 AC: 1 AN: 1450

Ashkenazi Jewish (ASJ) AF: 0.000467 AC: 1 AN: 2142

East Asian (EAS) AF: 0.000248 AC: 1 AN: 4032

South Asian (SAS) AF: 0.00 AC: 0 AN: 614

European-Finnish (FIN) AF: 0.0158 AC: 73 AN: 4630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 332

European-Non Finnish (NFE) AF: 0.00787 AC: 290 AN: 36826

Other (OTH) AF: 0.00460 AC: 17 AN: 3696

GnomAD4 genome AF: 0.00648 AC: 986 AN: 152212 Hom.: 12 Cov.: 32 AF XY: 0.00680 AC XY: 506 AN XY: 74402

African (AFR) AF: 0.00128 AC: 53 AN: 41556

American (AMR) AF: 0.00222 AC: 34 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5142

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4818

European-Finnish (FIN) AF: 0.0202 AC: 214 AN: 10614

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00984 AC: 669 AN: 67978

Other (OTH) AF: 0.00378 AC: 8 AN: 2116

Alfa AF: 0.0139 Hom.: 5

Bravo AF: 0.00442

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	1	-	Developmental and epileptic encephalopathy, 12 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	20
DANN	Uncertain	0.98
PhyloP100		2.7
PromoterAI		-0.048	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Mutation Taster		=299/1	polymorphism

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: rs532302075; hg19: chr20-8112969;