Genetic Variant NM_032726.4:c.541-28T>C (chr2-218622619-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032726.4(PLCD4):c.541-28T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0365 in 1,501,908 control chromosomes in the GnomAD database, including 1,201 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 0.041 ( 168 hom., cov: 33)

Exomes 𝑓: 0.036 ( 1033 hom. )

Consequence

PLCD4
NM_032726.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0730

Publications

5 publications found

Variant links:

Genes affected

PLCD4 (HGNC:9062): (phospholipase C delta 4) This gene encodes a member of the delta class of phospholipase C enzymes. Phospholipase C enzymes play a critical role in many cellular processes by hydrolyzing phosphatidylinositol 4,5-bisphosphate into two intracellular second messengers, inositol 1,4,5-trisphosphate and diacylglycerol. Expression of this gene may be a marker for cancer. [provided by RefSeq, Jan 2011]

PLCD4 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCD4	NM_032726.4 link	c.541-28T>C		intron_variant	Intron 5 of 15	ENST00000450993.7	NP_116115.1	Q9BRC7-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PLCD4	ENST00000450993.7 link	c.541-28T>C	intron_variant	Intron 5 of 15	1	NM_032726.4	ENSP00000388631.2	Q9BRC7-1
PLCD4	ENST00000432688.5 link	c.541-28T>C	intron_variant	Intron 5 of 16	5		ENSP00000396185.1	C9JEA7
PLCD4	ENST00000417849.5 link	c.541-28T>C	intron_variant	Intron 5 of 16	5		ENSP00000396942.1	Q9BRC7-1

Frequencies

GnomAD3 genomes

AF:

0.0409

AC:

6226

AN:

152166

Hom.:

167

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0543

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0228

Gnomad ASJ

AF:

0.0334

Gnomad EAS

AF:

0.118

Gnomad SAS

AF:

0.0439

Gnomad FIN

AF:

0.0271

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0336

Gnomad OTH

AF:

0.0388

GnomAD2 exomes

AF:

0.0396

AC:

7870

AN:

198798

AF XY:

0.0396

show subpopulations

Gnomad AFR exome

AF:

0.0525

Gnomad AMR exome

AF:

0.0171

Gnomad ASJ exome

AF:

0.0320

Gnomad EAS exome

AF:

0.112

Gnomad FIN exome

AF:

0.0314

Gnomad NFE exome

AF:

0.0333

Gnomad OTH exome

AF:

0.0341

GnomAD4 exome

AF:

0.0360

AC:

48531

AN:

1349624

Hom.:

1033

Cov.:

AF XY:

0.0362

AC XY:

24196

AN XY:

667736

show subpopulations

African (AFR)

AF:

0.0545

AC:

1614

AN:

29626

American (AMR)

AF:

0.0186

AC:

534

AN:

28728

Ashkenazi Jewish (ASJ)

AF:

0.0328

AC:

745

AN:

22712

East Asian (EAS)

AF:

0.110

AC:

4190

AN:

37936

South Asian (SAS)

AF:

0.0423

AC:

3016

AN:

71372

European-Finnish (FIN)

AF:

0.0312

AC:

1589

AN:

50992

Middle Eastern (MID)

AF:

0.0273

AC:

147

AN:

5386

European-Non Finnish (NFE)

AF:

0.0330

AC:

34557

AN:

1047324

Other (OTH)

AF:

0.0385

AC:

2139

AN:

55548

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

2295

4590

6885

9180

11475

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1400

2800

4200

5600

7000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0409

AC:

6230

AN:

152284

Hom.:

168

Cov.:

AF XY:

0.0401

AC XY:

2984

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0542

AC:

2251

AN:

41546

American (AMR)

AF:

0.0229

AC:

350

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0334

AC:

116

AN:

3470

East Asian (EAS)

AF:

0.118

AC:

614

AN:

5190

South Asian (SAS)

AF:

0.0439

AC:

212

AN:

4826

European-Finnish (FIN)

AF:

0.0271

AC:

288

AN:

10612

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0336

AC:

2285

AN:

68038

Other (OTH)

AF:

0.0384

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

317

633

950

1266

1583

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0351

Hom.:

Bravo

AF:

0.0417

Asia WGS

AF:

0.0690

AC:

240

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.7

(source)

DANN

Benign

0.66

PhyloP100

0.073

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over