14-104927219-G-C

Variant names:

• chr14-104927219-G-C
• rs2841280
• NM_138790.5:c.79G>C

Variant summary

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

The NM_138790.5(PLD4):​c.79G>C​(p.Glu27Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 1,549,494 control chromosomes in the GnomAD database, including 164,635 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.41 (13878 hom., cov: 33)
  • Exomes 𝑓: 0.46 (150757 hom.)
• Consequence: PLD4 NM_138790.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 32 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=3.7715872E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLD4	NM_138790.5	c.79G>C	p.Glu27Gln	missense_variant	Exon 2 of 11	ENST00000392593.9	NP_620145.2
PLD4	NM_001308174.2	c.100G>C	p.Glu34Gln	missense_variant	Exon 2 of 11		NP_001295103.1
PLD4	XM_011536411.3	c.100G>C	p.Glu34Gln	missense_variant	Exon 2 of 11		XP_011534713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLD4	ENST00000392593.9	c.79G>C	p.Glu27Gln	missense_variant	Exon 2 of 11	1	NM_138790.5	ENSP00000376372.5

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62705 AN: 152028 Hom.: 13875 Cov.: 33

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.407

GnomAD2 exomes AF: 0.449 AC: 69774 AN: 155536 AF XY: 0.443

Gnomad AFR exome AF: 0.229

Gnomad AMR exome AF: 0.500

Gnomad ASJ exome AF: 0.340

Gnomad EAS exome AF: 0.566

Gnomad FIN exome AF: 0.592

Gnomad NFE exome AF: 0.444

Gnomad OTH exome AF: 0.411

GnomAD4 exome AF: 0.460 AC: 642751 AN: 1397348 Hom.: 150757 Cov.: 37 AF XY: 0.457 AC XY: 315397 AN XY: 689726

African (AFR) AF: 0.240 AC: 7619 AN: 31774

American (AMR) AF: 0.493 AC: 17242 AN: 34944

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 8592 AN: 24924

East Asian (EAS) AF: 0.602 AC: 21768 AN: 36154

South Asian (SAS) AF: 0.387 AC: 30523 AN: 78952

European-Finnish (FIN) AF: 0.594 AC: 28702 AN: 48300

Middle Eastern (MID) AF: 0.322 AC: 1807 AN: 5618

European-Non Finnish (NFE) AF: 0.465 AC: 501506 AN: 1078892

Other (OTH) AF: 0.432 AC: 24992 AN: 57790

GnomAD4 genome AF: 0.412 AC: 62731 AN: 152146 Hom.: 13878 Cov.: 33 AF XY: 0.417 AC XY: 31037 AN XY: 74366

African (AFR) AF: 0.252 AC: 10462 AN: 41500

American (AMR) AF: 0.435 AC: 6659 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1176 AN: 3466

East Asian (EAS) AF: 0.577 AC: 2978 AN: 5164

South Asian (SAS) AF: 0.397 AC: 1916 AN: 4832

European-Finnish (FIN) AF: 0.595 AC: 6304 AN: 10600

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.468 AC: 31799 AN: 67966

Other (OTH) AF: 0.407 AC: 861 AN: 2114

Alfa AF: 0.438 Hom.: 4882

Bravo AF: 0.396

TwinsUK AF: 0.456 AC: 1690

ALSPAC AF: 0.458 AC: 1765

ESP6500AA AF: 0.223 AC: 832

ESP6500EA AF: 0.442 AC: 3591

ExAC AF: 0.343 AC: 36709

Asia WGS AF: 0.428 AC: 1487 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.3
DANN	Benign	0.29
DEOGEN2	Benign	0.0	.;T;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.37	T;T;T;T
MetaRNN	Benign	0.000038	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	.;.;L;.
PhyloP100		-1.2
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.0	.;N;N;N
REVEL	Benign	0.0
Sift	Pathogenic	0.0	.;T;T;T
Sift4G	Pathogenic	0.0	.;T;T;T
Vest4		0.0
ClinPred		0.0036	T
GERP RS		1.2
Varity_R		0.079
gMVP		0.25
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: rs2841280; hg19: chr14-105393556; COSMIC: COSV66914707; COSMIC: COSV66914707;