14-74942064-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002632.6(PGF):c.*642C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0173 in 153,184 control chromosomes in the GnomAD database, including 57 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 0.017 (57 hom., cov: 33)
  • Exomes 𝑓: 0.0041 (0 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=-0.84).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0173 (2639/152214) while in subpopulation AFR AF= 0.0333 (1385/41536). AF 95% confidence interval is 0.0319. There are 57 homozygotes in gnomad4. There are 1287 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 2628 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0173 AC: 2628 AN: 152096 Hom.: 56 Cov.: 33

Gnomad AFR AF: 0.0333

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0279

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00636

Gnomad SAS AF: 0.0311

Gnomad FIN AF: 0.00236

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00835

Gnomad OTH AF: 0.0144

GnomAD4 exome AF: 0.00412 AC: 4 AN: 970 Hom.: 0 Cov.: 0 AF XY: 0.00464 AC XY: 3 AN XY: 646

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.100

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0161

Gnomad4 NFE exome AF: 0.00276

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0173 AC: 2639 AN: 152214 Hom.: 57 Cov.: 33 AF XY: 0.0173 AC XY: 1287 AN XY: 74410

Gnomad4 AFR AF: 0.0333

Gnomad4 AMR AF: 0.0280

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00657

Gnomad4 SAS AF: 0.0315

Gnomad4 FIN AF: 0.00236

Gnomad4 NFE AF: 0.00837

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.000635 Hom.: 460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.34
Dann	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;