chr14-74955472-C-T

Position:

• chr14-74955472-C-T

Variant summary

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

The NM_002632.6(PGF):​c.-230G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 388,668 control chromosomes in the GnomAD database, including 172 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 0.023 (146 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (26 hom.)
• Consequence: PGF NM_002632.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.255

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=-0.69).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGF	NM_002632.6	c.-230G>A		5_prime_UTR_variant	1/7	ENST00000555567.6
PGF	NM_001207012.1	c.-230G>A		5_prime_UTR_variant	1/6
PGF	NM_001293643.1	c.-230G>A		5_prime_UTR_variant	1/7
PGF	XM_047431476.1	c.-230G>A		5_prime_UTR_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGF	ENST00000555567.6	c.-230G>A		5_prime_UTR_variant	1/7	1	NM_002632.6	P4

Frequencies

GnomAD3 genomes AF: 0.0227 AC: 3449 AN: 152096 Hom.: 146 Cov.: 32

Gnomad AFR AF: 0.0791

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00844

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000177

Gnomad OTH AF: 0.0134

GnomAD4 exome AF: 0.00292 AC: 690 AN: 236458 Hom.: 26 Cov.: 0 AF XY: 0.00242 AC XY: 292 AN XY: 120428

Gnomad4 AFR exome AF: 0.0787

Gnomad4 AMR exome AF: 0.00561

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000106

Gnomad4 OTH exome AF: 0.00600

GnomAD4 genome AF: 0.0227 AC: 3454 AN: 152210 Hom.: 146 Cov.: 32 AF XY: 0.0210 AC XY: 1560 AN XY: 74408

Gnomad4 AFR AF: 0.0790

Gnomad4 AMR AF: 0.00843

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000177

Gnomad4 OTH AF: 0.0133

Alfa AF: 0.0157 Hom.: 11

Bravo AF: 0.0259

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	10
DANN	Benign	0.75

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: rs11542848; hg19: chr14-75422175;