rs10485729

Variant names:

• chr20-9184511-A-G
• rs10485729
• NM_001377142.1:c.-78-32879A>G

Your query was ambiguous. Multiple possible variants found:

• chr20-9184511-A-G
• chr20-9184511-A-T

Variant summary

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

The NM_001377142.1(PLCB4):​c.-78-32879A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 151,070 control chromosomes in the GnomAD database, including 2,990 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 0.19 (2990 hom., cov: 30)
• Consequence: PLCB4 NM_001377142.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310
• Publications: 1 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCB4	NM_001377142.1	c.-78-32879A>G		intron_variant	Intron 2 of 39	ENST00000378473.9	NP_001364071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCB4	ENST00000378473.9	c.-78-32879A>G		intron_variant	Intron 2 of 39	1	NM_001377142.1	ENSP00000367734.5

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29023 AN: 150960 Hom.: 2976 Cov.: 30

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.192 AC: 29068 AN: 151070 Hom.: 2990 Cov.: 30 AF XY: 0.193 AC XY: 14238 AN XY: 73690

African (AFR) AF: 0.232 AC: 9571 AN: 41176

American (AMR) AF: 0.268 AC: 4048 AN: 15084

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 450 AN: 3466

East Asian (EAS) AF: 0.286 AC: 1458 AN: 5104

South Asian (SAS) AF: 0.207 AC: 985 AN: 4748

European-Finnish (FIN) AF: 0.134 AC: 1389 AN: 10340

Middle Eastern (MID) AF: 0.103 AC: 30 AN: 292

European-Non Finnish (NFE) AF: 0.158 AC: 10699 AN: 67858

Other (OTH) AF: 0.173 AC: 362 AN: 2092

Alfa AF: 0.181 Hom.: 1233

Bravo AF: 0.206

Asia WGS AF: 0.211 AC: 735 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	10
DANN	Benign	0.71
PhyloP100		0.031
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10485729; hg19: chr20-9165158;