NM_015192.4:c.3337-69G>A

Variant names:

• chr20-8790106-G-A
• rs45541432
• NM_015192.4:c.3337-69G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_015192.4(PLCB1):​c.3337-69G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000204 in 1,033,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00020 (0 hom.)
• Consequence: PLCB1 NM_015192.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0340
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 20-8790106-G-A is Benign according to our data. Variant chr20-8790106-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 522926.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00021 (32/152120) while in subpopulation EAS AF = 0.0029 (15/5178). AF 95% confidence interval is 0.00179. There are 0 homozygotes in GnomAd4. There are 22 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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.3337-69G>A		intron	N/A	NP_056007.1	Q9NQ66-1
	PLCB1	NM_182734.3		c.3337-69G>A		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.3337-69G>A		intron	N/A	ENSP00000338185.6	Q9NQ66-1
	PLCB1	ENST00000378637.6	TSL:1	c.3337-69G>A		intron	N/A	ENSP00000367904.2	Q9NQ66-2
	PLCB1	ENST00000378641.7	TSL:1	c.3337-69G>A		intron	N/A	ENSP00000367908.3	Q9NQ66-2

Frequencies

GnomAD3 genomes AF: 0.000211 AC: 32 AN: 152002 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000203 AC: 179 AN: 881796 Hom.: 0 AF XY: 0.000217 AC XY: 99 AN XY: 456704

African (AFR) AF: 0.0000480 AC: 1 AN: 20846

American (AMR) AF: 0.00 AC: 0 AN: 34148

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21044

East Asian (EAS) AF: 0.00214 AC: 71 AN: 33126

South Asian (SAS) AF: 0.00 AC: 0 AN: 67650

European-Finnish (FIN) AF: 0.000103 AC: 5 AN: 48676

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4578

European-Non Finnish (NFE) AF: 0.000150 AC: 92 AN: 611416

Other (OTH) AF: 0.000248 AC: 10 AN: 40312

GnomAD4 genome AF: 0.000210 AC: 32 AN: 152120 Hom.: 0 Cov.: 32 AF XY: 0.000296 AC XY: 22 AN XY: 74366

African (AFR) AF: 0.00 AC: 0 AN: 41510

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00290 AC: 15 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 67988

Other (OTH) AF: 0.00 AC: 0 AN: 2104

Alfa AF: 0.000635 Hom.: 0

Bravo AF: 0.000264

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Developmental and epileptic encephalopathy, 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.12
DANN	Benign	0.61
PhyloP100		-0.034
PromoterAI		0.014	Neutral
Mutation Taster		=100/0	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: rs45541432; hg19: chr20-8770753;