14-74942064-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002632.6(PGF):c.*642C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.09 in 153,160 control chromosomes in the GnomAD database, including 854 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 0.090 (850 hom., cov: 33)
  • Exomes 𝑓: 0.087 (4 hom.)
• Consequence: PGF NM_002632.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.197

Genes affected

PGF (HGNC:8893): (placental growth factor) Enables growth factor activity. Involved in positive regulation of cell population proliferation. Predicted to be located in extracellular region. Predicted to be active in extracellular space. Implicated in several diseases, including brain ischemia; diabetic neuropathy; glioblastoma; myocardial infarction; and pancreatic endocrine carcinoma. Biomarker of several diseases, including artery disease (multiple); autoimmune disease of musculoskeletal system (multiple); epilepsy (multiple); limited scleroderma; and pancreatic endocrine carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGF	NM_002632.6	c.*642C>A		3_prime_UTR_variant	7/7	ENST00000555567.6
PGF	NM_001207012.1	c.*642C>A		3_prime_UTR_variant	6/6
PGF	NM_001293643.1	c.*642C>A		3_prime_UTR_variant	7/7
PGF	XM_047431476.1	c.*642C>A		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGF	ENST00000555567.6	c.*642C>A		3_prime_UTR_variant	7/7	1	NM_002632.6	P4
PGF	ENST00000553716.5	c.*642C>A		3_prime_UTR_variant	6/6	1		A1
PGF	ENST00000238607.10	c.*642C>A		3_prime_UTR_variant	7/7	3		A1

Frequencies

GnomAD3 genomes AF: 0.0901 AC: 13707 AN: 152080 Hom.: 851 Cov.: 33

Gnomad AFR AF: 0.0203

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0981

Gnomad ASJ AF: 0.0828

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0834

GnomAD4 exome AF: 0.0873 AC: 84 AN: 962 Hom.: 4 Cov.: 0 AF XY: 0.0891 AC XY: 57 AN XY: 640

Gnomad4 AFR exome AF: 0.100

Gnomad4 AMR exome AF: 0.100

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0714

Gnomad4 SAS exome AF: 0.227

Gnomad4 FIN exome AF: 0.194

Gnomad4 NFE exome AF: 0.0627

Gnomad4 OTH exome AF: 0.0870

GnomAD4 genome AF: 0.0901 AC: 13707 AN: 152198 Hom.: 850 Cov.: 33 AF XY: 0.0974 AC XY: 7246 AN XY: 74400

Gnomad4 AFR AF: 0.0203

Gnomad4 AMR AF: 0.0983

Gnomad4 ASJ AF: 0.0828

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.0821

Alfa AF: 0.0909 Hom.: 460

Bravo AF: 0.0798

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.89
Dann	Benign	0.59

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

LitVar

Other links and lift over

dbSNP: rs1042886; hg19: chr14-75408767;