rs8115510

Variant names:

• chr20-9333294-T-C
• rs8115510
• NM_001377142.1:c.85-3832T>C

Your query was ambiguous. Multiple possible variants found:

• chr20-9333294-T-C
• chr20-9333294-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377142.1(PLCB4):​c.85-3832T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0631 in 151,640 control chromosomes in the GnomAD database, including 318 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.063 (318 hom., cov: 32)
• Consequence: PLCB4 NM_001377142.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09
• Publications: 4 publications found

Genes affected

PLCB4 (HGNC:9059): (phospholipase C beta 4) 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 in the retina. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2010]

PLCB4 Gene-Disease associations (from GenCC):

• auriculocondylar syndrome 2

  Inheritance: AD, AR, SD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Illumina, Ambry Genetics
• auriculocondylar syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000307219 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCB4	NM_001377142.1	c.85-3832T>C		intron_variant	Intron 4 of 39	ENST00000378473.9	NP_001364071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCB4	ENST00000378473.9	c.85-3832T>C		intron_variant	Intron 4 of 39	1	NM_001377142.1	ENSP00000367734.5

Frequencies

GnomAD3 genomes AF: 0.0632 AC: 9569 AN: 151520 Hom.: 318 Cov.: 32

Gnomad AFR AF: 0.0649

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0593

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.000582

Gnomad SAS AF: 0.0656

Gnomad FIN AF: 0.0560

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0657

Gnomad OTH AF: 0.0744

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

GnomAD4 genome AF: 0.0631 AC: 9563 AN: 151640 Hom.: 318 Cov.: 32 AF XY: 0.0628 AC XY: 4653 AN XY: 74084

African (AFR) AF: 0.0647 AC: 2671 AN: 41292

American (AMR) AF: 0.0593 AC: 903 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 361 AN: 3462

East Asian (EAS) AF: 0.000583 AC: 3 AN: 5144

South Asian (SAS) AF: 0.0646 AC: 309 AN: 4780

European-Finnish (FIN) AF: 0.0560 AC: 588 AN: 10508

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0657 AC: 4465 AN: 67920

Other (OTH) AF: 0.0737 AC: 155 AN: 2104

Alfa AF: 0.0676 Hom.: 629

Bravo AF: 0.0649

Asia WGS AF: 0.0340 AC: 119 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.48
DANN	Benign	0.83
PhyloP100		-2.1
Mutation Taster		=100/0	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: rs8115510; hg19: chr20-9313941;