20-8902709-TA-TAAA

Variant names:

• chr20-8902709-T-TAA
• rs11087829
• ENST00000487210.5:n.*20-59487_*20-59486insAA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The ENST00000487210.5(PLCB1):​n.*20-59487_*20-59486insAA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.00065 (0 hom., cov: 0)
• Consequence: PLCB1 ENST00000487210.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.691
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000646 (94/145408) while in subpopulation AFR AF = 0.00221 (87/39444). AF 95% confidence interval is 0.00183. There are 0 homozygotes in GnomAd4. There are 54 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCB1	ENST00000487210.5	n.*20-59487_*20-59486insAA		intron_variant	Intron 24 of 26	1		ENSP00000431704.1
PLCB1	ENST00000635929.1	n.592-59487_592-59486insAA		intron_variant	Intron 6 of 9	5		ENSP00000490792.1

Frequencies

GnomAD3 genomes AF: 0.000647 AC: 94 AN: 145364 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00221

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000136

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000398

Gnomad SAS AF: 0.000222

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000150

Gnomad OTH AF: 0.000501

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.000646 AC: 94 AN: 145408 Hom.: 0 Cov.: 0 AF XY: 0.000767 AC XY: 54 AN XY: 70420

African (AFR) AF: 0.00221 AC: 87 AN: 39444

American (AMR) AF: 0.000136 AC: 2 AN: 14736

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3432

East Asian (EAS) AF: 0.000399 AC: 2 AN: 5012

South Asian (SAS) AF: 0.000223 AC: 1 AN: 4480

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8514

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.0000150 AC: 1 AN: 66600

Other (OTH) AF: 0.000498 AC: 1 AN: 2010

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.69

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11087829; hg19: chr20-8883356;