rs6118591

Variant names:

• chr20-9393873-T-C
• rs6118591
• NM_001377142.1:c.1414+195T>C

Variant summary

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

The NM_001377142.1(PLCB4):​c.1414+195T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 151,958 control chromosomes in the GnomAD database, including 7,489 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 0.31 (7489 hom., cov: 32)
• Consequence: PLCB4 NM_001377142.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.864
• Publications: 7 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCB4	NM_001377142.1	c.1414+195T>C		intron_variant	Intron 18 of 39	ENST00000378473.9	NP_001364071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCB4	ENST00000378473.9	c.1414+195T>C		intron_variant	Intron 18 of 39	1	NM_001377142.1	ENSP00000367734.5

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47358 AN: 151842 Hom.: 7479 Cov.: 32

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.312 AC: 47388 AN: 151958 Hom.: 7489 Cov.: 32 AF XY: 0.311 AC XY: 23094 AN XY: 74282

African (AFR) AF: 0.360 AC: 14902 AN: 41412

American (AMR) AF: 0.280 AC: 4270 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 940 AN: 3462

East Asian (EAS) AF: 0.403 AC: 2080 AN: 5162

South Asian (SAS) AF: 0.309 AC: 1487 AN: 4808

European-Finnish (FIN) AF: 0.236 AC: 2492 AN: 10572

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20196 AN: 67956

Other (OTH) AF: 0.302 AC: 637 AN: 2110

Alfa AF: 0.302 Hom.: 10006

Bravo AF: 0.320

Asia WGS AF: 0.360 AC: 1250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.5
DANN	Benign	0.81
PhyloP100		0.86
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: rs6118591; hg19: chr20-9374520;