rs16994453

Variant names:

• chr20-8150296-C-T
• rs16994453
• NM_015192.4:c.102C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-8150296-C-T
• chr20-8150296-C-A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_015192.4(PLCB1):​c.102C>T​(p.Asp34Asp) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,427,118 control chromosomes in the GnomAD database, including 17,701 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2571 hom., cov: 32)
  • Exomes 𝑓: 0.15 (15130 hom.)
• Consequence: PLCB1 NM_015192.4 splice_region, synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.640
• Publications: 22 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 20-8150296-C-T is Benign according to our data. Variant chr20-8150296-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 129899.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.64 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.227 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.102C>T	p.Asp34Asp	splice_region synonymous	Exon 2 of 32	NP_056007.1	Q9NQ66-1
	PLCB1	NM_182734.3		c.102C>T	p.Asp34Asp	splice_region synonymous	Exon 2 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.102C>T	p.Asp34Asp	splice_region synonymous	Exon 2 of 32	ENSP00000338185.6	Q9NQ66-1
	PLCB1	ENST00000378637.6	TSL:1	c.102C>T	p.Asp34Asp	splice_region synonymous	Exon 2 of 32	ENSP00000367904.2	Q9NQ66-2
	PLCB1	ENST00000378641.7	TSL:1	c.102C>T	p.Asp34Asp	splice_region synonymous	Exon 2 of 33	ENSP00000367908.3	Q9NQ66-2

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27307 AN: 151958 Hom.: 2569 Cov.: 32

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.156

GnomAD2 exomes AF: 0.159 AC: 37044 AN: 233688 AF XY: 0.160

Gnomad AFR exome AF: 0.231

Gnomad AMR exome AF: 0.0893

Gnomad ASJ exome AF: 0.121

Gnomad EAS exome AF: 0.144

Gnomad FIN exome AF: 0.161

Gnomad NFE exome AF: 0.164

Gnomad OTH exome AF: 0.147

GnomAD4 exome AF: 0.150 AC: 191641 AN: 1275042 Hom.: 15130 Cov.: 18 AF XY: 0.153 AC XY: 98681 AN XY: 642920

African (AFR) AF: 0.212 AC: 6108 AN: 28770

American (AMR) AF: 0.0924 AC: 3603 AN: 38978

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 2751 AN: 24460

East Asian (EAS) AF: 0.180 AC: 6819 AN: 37944

South Asian (SAS) AF: 0.189 AC: 14735 AN: 78100

European-Finnish (FIN) AF: 0.166 AC: 8780 AN: 52828

Middle Eastern (MID) AF: 0.117 AC: 629 AN: 5370

European-Non Finnish (NFE) AF: 0.147 AC: 140401 AN: 954736

Other (OTH) AF: 0.145 AC: 7815 AN: 53856

GnomAD4 genome AF: 0.180 AC: 27327 AN: 152076 Hom.: 2571 Cov.: 32 AF XY: 0.177 AC XY: 13124 AN XY: 74316

African (AFR) AF: 0.230 AC: 9562 AN: 41492

American (AMR) AF: 0.114 AC: 1740 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 403 AN: 3470

East Asian (EAS) AF: 0.148 AC: 766 AN: 5178

South Asian (SAS) AF: 0.207 AC: 996 AN: 4818

European-Finnish (FIN) AF: 0.154 AC: 1633 AN: 10586

Middle Eastern (MID) AF: 0.110 AC: 32 AN: 292

European-Non Finnish (NFE) AF: 0.173 AC: 11733 AN: 67920

Other (OTH) AF: 0.156 AC: 329 AN: 2112

Alfa AF: 0.171 Hom.: 3907

Bravo AF: 0.175

Asia WGS AF: 0.154 AC: 533 AN: 3466

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	1	Developmental and epileptic encephalopathy, 12 (1)
-	-	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	-0.36
CADD	Benign	14
DANN	Benign	0.72
PhyloP100		0.64
PromoterAI		0.0032	Neutral
Mutation Taster		=97/3	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: rs16994453; hg19: chr20-8130943; COSMIC: COSV62051168; COSMIC: COSV62051168;