rs3761170

Variant names:

• chr20-8737066-G-A
• rs3761170
• NM_015192.4:c.2082G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-8737066-G-A
• chr20-8737066-G-T
• chr20-8737066-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_015192.4(PLCB1):​c.2082G>A​(p.Gly694Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0687 in 1,612,662 control chromosomes in the GnomAD database, including 4,673 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G694G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.063 (410 hom., cov: 33)
  • Exomes 𝑓: 0.069 (4263 hom.)
• Consequence: PLCB1 NM_015192.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.276
• Publications: 15 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 20-8737066-G-A is Benign according to our data. Variant chr20-8737066-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 129903.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.276 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.152 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.2082G>A	p.Gly694Gly	synonymous	Exon 20 of 32	NP_056007.1	Q9NQ66-1
	PLCB1	NM_182734.3		c.2082G>A	p.Gly694Gly	synonymous	Exon 20 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.2082G>A	p.Gly694Gly	synonymous	Exon 20 of 32	ENSP00000338185.6	Q9NQ66-1
	PLCB1	ENST00000378637.6	TSL:1	c.2082G>A	p.Gly694Gly	synonymous	Exon 20 of 32	ENSP00000367904.2	Q9NQ66-2
	PLCB1	ENST00000378641.7	TSL:1	c.2082G>A	p.Gly694Gly	synonymous	Exon 20 of 33	ENSP00000367908.3	Q9NQ66-2

Frequencies

GnomAD3 genomes AF: 0.0633 AC: 9628 AN: 152062 Hom.: 405 Cov.: 33

Gnomad AFR AF: 0.0350

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0934

Gnomad ASJ AF: 0.0978

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.0388

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0629

Gnomad OTH AF: 0.0856

GnomAD2 exomes AF: 0.0799 AC: 20068 AN: 251248 AF XY: 0.0837

Gnomad AFR exome AF: 0.0348

Gnomad AMR exome AF: 0.0838

Gnomad ASJ exome AF: 0.0921

Gnomad EAS exome AF: 0.119

Gnomad FIN exome AF: 0.0411

Gnomad NFE exome AF: 0.0644

Gnomad OTH exome AF: 0.0747

GnomAD4 exome AF: 0.0692 AC: 101115 AN: 1460482 Hom.: 4263 Cov.: 30 AF XY: 0.0721 AC XY: 52391 AN XY: 726610

African (AFR) AF: 0.0325 AC: 1087 AN: 33460

American (AMR) AF: 0.0848 AC: 3793 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.0911 AC: 2378 AN: 26116

East Asian (EAS) AF: 0.143 AC: 5676 AN: 39634

South Asian (SAS) AF: 0.155 AC: 13335 AN: 86174

European-Finnish (FIN) AF: 0.0397 AC: 2121 AN: 53402

Middle Eastern (MID) AF: 0.0938 AC: 540 AN: 5758

European-Non Finnish (NFE) AF: 0.0608 AC: 67524 AN: 1110910

Other (OTH) AF: 0.0773 AC: 4661 AN: 60324

GnomAD4 genome AF: 0.0634 AC: 9641 AN: 152180 Hom.: 410 Cov.: 33 AF XY: 0.0650 AC XY: 4838 AN XY: 74410

African (AFR) AF: 0.0351 AC: 1456 AN: 41520

American (AMR) AF: 0.0933 AC: 1425 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0978 AC: 339 AN: 3468

East Asian (EAS) AF: 0.137 AC: 707 AN: 5172

South Asian (SAS) AF: 0.162 AC: 780 AN: 4822

European-Finnish (FIN) AF: 0.0388 AC: 412 AN: 10608

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0629 AC: 4275 AN: 67994

Other (OTH) AF: 0.0922 AC: 195 AN: 2114

Alfa AF: 0.0534 Hom.: 191

Bravo AF: 0.0617

Asia WGS AF: 0.158 AC: 549 AN: 3478

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	-0.53
CADD	Benign	6.6
DANN	Benign	0.49
PhyloP100		-0.28
PromoterAI		0.0019	Neutral
Mutation Taster		=99/1	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: rs3761170; hg19: chr20-8717713; COSMIC: COSV106477258; COSMIC: COSV106477258;