20-9244143-G-A

Variant names:

• chr20-9244143-G-A
• rs2224361
• NM_001377142.1:c.-16+26691G>A

Variant summary

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

The ENST00000378473.9(PLCB4):​c.-16+26691G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.971 in 152,192 control chromosomes in the GnomAD database, including 71,735 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 0.97 (71735 hom., cov: 30)
• Consequence: PLCB4 ENST00000378473.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000378473.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCB4	NM_001377142.1	MANE Select	c.-16+26691G>A		intron	N/A	NP_001364071.1
	PLCB4	NM_001377143.1		c.-16+26691G>A		intron	N/A	NP_001364072.1
	PLCB4	NM_000933.4		c.-16+26691G>A		intron	N/A	NP_000924.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCB4	ENST00000378473.9	TSL:1 MANE Select	c.-16+26691G>A		intron	N/A	ENSP00000367734.5
	PLCB4	ENST00000278655.9	TSL:1	c.-16+26691G>A		intron	N/A	ENSP00000278655.5
	PLCB4	ENST00000685298.1		c.-16+26691G>A		intron	N/A	ENSP00000509390.1

Frequencies

GnomAD3 genomes AF: 0.971 AC: 147601 AN: 152074 Hom.: 71672 Cov.: 30

Gnomad AFR AF: 0.993

Gnomad AMI AF: 0.931

Gnomad AMR AF: 0.982

Gnomad ASJ AF: 0.983

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.980

Gnomad FIN AF: 0.958

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.953

Gnomad OTH AF: 0.981

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

GnomAD4 genome AF: 0.971 AC: 147724 AN: 152192 Hom.: 71735 Cov.: 30 AF XY: 0.971 AC XY: 72274 AN XY: 74408

African (AFR) AF: 0.993 AC: 41213 AN: 41522

American (AMR) AF: 0.982 AC: 14996 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.983 AC: 3413 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5156 AN: 5162

South Asian (SAS) AF: 0.980 AC: 4729 AN: 4824

European-Finnish (FIN) AF: 0.958 AC: 10168 AN: 10610

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.953 AC: 64833 AN: 68012

Other (OTH) AF: 0.982 AC: 2077 AN: 2116

Alfa AF: 0.956 Hom.: 49496

Bravo AF: 0.975

Asia WGS AF: 0.989 AC: 3439 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.010
DANN	Benign	0.35
PhyloP100		-1.3
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: rs2224361; hg19: chr20-9224790;