rs2268613

Positions:

• chr14-74941797-G-A
• chr14-74941797-G-C

Variant summary

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

The 14-74941797-G-A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 152,474 control chromosomes in the GnomAD database, including 38,986 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 0.69 (38848 hom., cov: 31)
  • Exomes 𝑓: 0.77 (138 hom.)
• Consequence: PGF ENST00000555567.6 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGF	NM_002632.6			downstream_gene_variant		ENST00000555567.6	NP_002623.2
PGF	NM_001207012.1			downstream_gene_variant			NP_001193941.1
PGF	NM_001293643.1			downstream_gene_variant			NP_001280572.1
PGF	XM_047431476.1			downstream_gene_variant			XP_047287432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGF	ENST00000555567.6			downstream_gene_variant		1	NM_002632.6	ENSP00000451040	P4
PGF	ENST00000553716.5			downstream_gene_variant		1		ENSP00000451413	A1

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105584 AN: 151888 Hom.: 38853 Cov.: 31

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.836

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.865

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.742

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.729

GnomAD4 exome AF: 0.769 AC: 360 AN: 468 Hom.: 138 Cov.: 0 AF XY: 0.774 AC XY: 223 AN XY: 288

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.756

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.667

GnomAD4 genome AF: 0.695 AC: 105597 AN: 152006 Hom.: 38848 Cov.: 31 AF XY: 0.695 AC XY: 51658 AN XY: 74298

Gnomad4 AFR AF: 0.436

Gnomad4 AMR AF: 0.776

Gnomad4 ASJ AF: 0.865

Gnomad4 EAS AF: 0.851

Gnomad4 SAS AF: 0.688

Gnomad4 FIN AF: 0.742

Gnomad4 NFE AF: 0.803

Gnomad4 OTH AF: 0.733

Alfa AF: 0.795 Hom.: 95901

Bravo AF: 0.687

Asia WGS AF: 0.742 AC: 2580 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.11
DANN	Benign	0.65

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2268613; hg19: chr14-75408500;