Genetic Variant PLD4:c.-323C>T (chr14-104924668-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_138790.5(PLD4):c.-323C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 152,168 control chromosomes in the GnomAD database, including 14,087 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 0.42 ( 14076 hom., cov: 32)

Exomes 𝑓: 0.42 ( 11 hom. )

Consequence

PLD4
NM_138790.5 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.97

Publications

50 publications found

Variant links:

COSMIC-nc: COSV66915929

Genes affected

PLD4 (HGNC:23792): (phospholipase D family member 4) Predicted to enable single-stranded DNA 5'-3' exodeoxyribonuclease activity. Predicted to be involved in hematopoietic progenitor cell differentiation; phagocytosis; and regulation of cytokine production involved in inflammatory response. Predicted to be located in early endosome and endoplasmic reticulum membrane. Predicted to be active in several cellular components, including endoplasmic reticulum; phagocytic vesicle; and trans-Golgi network membrane. [provided by Alliance of Genome Resources, Apr 2022]

PLD4 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=-0.93).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138790.5. 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
	PLD4	NM_138790.5	MANE Select	c.-323C>T		upstream_gene	N/A	NP_620145.2	Q96BZ4
	PLD4	NM_001308174.2		c.-340C>T		upstream_gene	N/A	NP_001295103.1	F5H2B5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PLD4	ENST00000392593.9	TSL:1 MANE Select	c.-323C>T	upstream_gene	N/A	ENSP00000376372.5	Q96BZ4
PLD4	ENST00000540372.5	TSL:2	c.-340C>T	upstream_gene	N/A	ENSP00000438677.1	F5H2B5
PLD4	ENST00000862746.1		c.-412C>T	upstream_gene	N/A	ENSP00000532805.1

Frequencies

GnomAD3 genomes

AF:

0.416

AC:

63144

AN:

151958

Hom.:

14073

Cov.:

show subpopulations

Gnomad AFR

AF:

0.256

Gnomad AMI

AF:

0.598

Gnomad AMR

AF:

0.449

Gnomad ASJ

AF:

0.349

Gnomad EAS

AF:

0.598

Gnomad SAS

AF:

0.422

Gnomad FIN

AF:

0.590

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.465

Gnomad OTH

AF:

0.419

GnomAD4 exome

AF:

0.424

AC:

AN:

Hom.:

AF XY:

0.392

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.419

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.534

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.415

AC:

63166

AN:

152076

Hom.:

14076

Cov.:

AF XY:

0.422

AC XY:

31331

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.256

AC:

10624

AN:

41498

American (AMR)

AF:

0.449

AC:

6853

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.349

AC:

1213

AN:

3472

East Asian (EAS)

AF:

0.598

AC:

3090

AN:

5170

South Asian (SAS)

AF:

0.421

AC:

2033

AN:

4824

European-Finnish (FIN)

AF:

0.590

AC:

6234

AN:

10568

Middle Eastern (MID)

AF:

0.374

AC:

110

AN:

294

European-Non Finnish (NFE)

AF:

0.465

AC:

31580

AN:

67958

Other (OTH)

AF:

0.419

AC:

884

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1824

3649

5473

7298

9122

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

604

1208

1812

2416

3020

<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:

0.441

Hom.:

59781

Bravo

AF:

0.400

Asia WGS

AF:

0.448

AC:

1557

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.085

(source)

DANN

Benign

0.66

PhyloP100

-2.0

PromoterAI

0.022

Neutral

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over