NM_001377142.1:c.370-143A>G

Variant names:

• chr20-9362753-A-G
• rs41309925
• NM_001377142.1:c.370-143A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001377142.1(PLCB4):​c.370-143A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0339 in 628,034 control chromosomes in the GnomAD database, including 535 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (106 hom., cov: 33)
  • Exomes 𝑓: 0.035 (429 hom.)
• Consequence: PLCB4 NM_001377142.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.615
• Publications: 0 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, SD, AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, Illumina
• auriculocondylar syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 20-9362753-A-G is Benign according to our data. Variant chr20-9362753-A-G is described in ClinVar as Benign. ClinVar VariationId is 1275561.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0295 (4495/152324) while in subpopulation NFE AF = 0.0471 (3201/68024). AF 95% confidence interval is 0.0457. There are 106 homozygotes in GnomAd4. There are 2156 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 106 AD,AR,SD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377142.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCB4	NM_001377142.1	MANE Select	c.370-143A>G		intron	N/A	NP_001364071.1	A0A7P0MRI8
	PLCB4	NM_001377143.1		c.370-143A>G		intron	N/A	NP_001364072.1	A0A7P0MRI8
	PLCB4	NM_000933.4		c.370-143A>G		intron	N/A	NP_000924.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCB4	ENST00000378473.9	TSL:1 MANE Select	c.370-143A>G		intron	N/A	ENSP00000367734.5	A0A7P0MRI8
	PLCB4	ENST00000278655.9	TSL:1	c.370-143A>G		intron	N/A	ENSP00000278655.5	A0A8I5KRP3
	PLCB4	ENST00000946820.1		c.370-143A>G		intron	N/A	ENSP00000616879.1

Frequencies

GnomAD3 genomes AF: 0.0295 AC: 4496 AN: 152206 Hom.: 106 Cov.: 33

Gnomad AFR AF: 0.00741

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0230

Gnomad ASJ AF: 0.00664

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0120

Gnomad FIN AF: 0.0478

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0471

Gnomad OTH AF: 0.0201

GnomAD4 exome AF: 0.0353 AC: 16773 AN: 475710 Hom.: 429 AF XY: 0.0340 AC XY: 8655 AN XY: 254218

African (AFR) AF: 0.00826 AC: 107 AN: 12954

American (AMR) AF: 0.0166 AC: 393 AN: 23656

Ashkenazi Jewish (ASJ) AF: 0.00761 AC: 116 AN: 15238

East Asian (EAS) AF: 0.00 AC: 0 AN: 31066

South Asian (SAS) AF: 0.0124 AC: 601 AN: 48600

European-Finnish (FIN) AF: 0.0453 AC: 1403 AN: 30960

Middle Eastern (MID) AF: 0.00530 AC: 13 AN: 2454

European-Non Finnish (NFE) AF: 0.0470 AC: 13327 AN: 283742

Other (OTH) AF: 0.0301 AC: 813 AN: 27040

GnomAD4 genome AF: 0.0295 AC: 4495 AN: 152324 Hom.: 106 Cov.: 33 AF XY: 0.0289 AC XY: 2156 AN XY: 74482

African (AFR) AF: 0.00738 AC: 307 AN: 41580

American (AMR) AF: 0.0230 AC: 352 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00664 AC: 23 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.0120 AC: 58 AN: 4830

European-Finnish (FIN) AF: 0.0478 AC: 508 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0471 AC: 3201 AN: 68024

Other (OTH) AF: 0.0199 AC: 42 AN: 2112

Alfa AF: 0.0448 Hom.: 212

Bravo AF: 0.0259

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.55
PhyloP100		0.61
Mutation Taster		=100/0	polymorphism

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: rs41309925; hg19: chr20-9343400;