rs2582532

Variant names:

• chr14-104926500-T-C
• rs2582532
• NM_138790.5:c.1-641T>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.1-641T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.924 in 152,166 control chromosomes in the GnomAD database, including 65,507 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 0.92 (65507 hom., cov: 31)
• Consequence: PLD4 NM_138790.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.73
• Publications: 18 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 (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.982 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLD4	NM_138790.5	c.1-641T>C		intron_variant	Intron 1 of 10	ENST00000392593.9	NP_620145.2
PLD4	NM_001308174.2	c.-17-603T>C		intron_variant	Intron 1 of 10		NP_001295103.1
PLD4	XM_011536411.3	c.-17-603T>C		intron_variant	Intron 1 of 10		XP_011534713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLD4	ENST00000392593.9	c.1-641T>C		intron_variant	Intron 1 of 10	1	NM_138790.5	ENSP00000376372.5

Frequencies

GnomAD3 genomes AF: 0.925 AC: 140570 AN: 152048 Hom.: 65469 Cov.: 31

Gnomad AFR AF: 0.862

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.836

Gnomad ASJ AF: 0.986

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.865

Gnomad FIN AF: 0.997

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.989

Gnomad OTH AF: 0.925

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

GnomAD4 genome AF: 0.924 AC: 140664 AN: 152166 Hom.: 65507 Cov.: 31 AF XY: 0.921 AC XY: 68514 AN XY: 74398

African (AFR) AF: 0.862 AC: 35766 AN: 41480

American (AMR) AF: 0.835 AC: 12769 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.986 AC: 3424 AN: 3472

East Asian (EAS) AF: 0.689 AC: 3549 AN: 5148

South Asian (SAS) AF: 0.866 AC: 4175 AN: 4820

European-Finnish (FIN) AF: 0.997 AC: 10591 AN: 10624

Middle Eastern (MID) AF: 0.983 AC: 289 AN: 294

European-Non Finnish (NFE) AF: 0.989 AC: 67244 AN: 68014

Other (OTH) AF: 0.921 AC: 1945 AN: 2112

Alfa AF: 0.960 Hom.: 106472

Bravo AF: 0.912

Asia WGS AF: 0.724 AC: 2522 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.59
DANN	Benign	0.31
PhyloP100		-3.7
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: rs2582532; hg19: chr14-105392837;