20-8902709-TA-TAAAA

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000487210.5(PLCB1):​n.*20-59487_*20-59486insAAA 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 0.0097 (27 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0097 (1411/145410) while in subpopulation AFR AF = 0.0307 (1210/39440). AF 95% confidence interval is 0.0292. There are 27 homozygotes in GnomAd4. There are 657 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 27 AD,AR gene

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_*20-59486insAAA		intron_variant	Intron 24 of 26	1		ENSP00000431704.1
PLCB1	ENST00000635929.1	n.592-59487_592-59486insAAA		intron_variant	Intron 6 of 9	5		ENSP00000490792.1

Frequencies

GnomAD3 genomes AF: 0.00971 AC: 1411 AN: 145366 Hom.: 27 Cov.: 0

Gnomad AFR AF: 0.0307

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00326

Gnomad ASJ AF: 0.000291

Gnomad EAS AF: 0.0209

Gnomad SAS AF: 0.00288

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000330

Gnomad OTH AF: 0.00651

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

GnomAD4 genome AF: 0.00970 AC: 1411 AN: 145410 Hom.: 27 Cov.: 0 AF XY: 0.00933 AC XY: 657 AN XY: 70424

African (AFR) AF: 0.0307 AC: 1210 AN: 39440

American (AMR) AF: 0.00326 AC: 48 AN: 14738

Ashkenazi Jewish (ASJ) AF: 0.000291 AC: 1 AN: 3432

East Asian (EAS) AF: 0.0208 AC: 104 AN: 5010

South Asian (SAS) AF: 0.00290 AC: 13 AN: 4480

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.000330 AC: 22 AN: 66604

Other (OTH) AF: 0.00647 AC: 13 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;