14-74942086-T-C

Position:

• chr14-74942086-T-C

Variant summary

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

The NM_002632.6(PGF):​c.*620A>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 0.204 in 153,076 control chromosomes in the GnomAD database, including 3,512 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 0.20 (3496 hom., cov: 33)
  • Exomes 𝑓: 0.14 (16 hom.)
• Consequence: PGF NM_002632.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180

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 (AFR) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGF	NM_002632.6	c.*620A>G		3_prime_UTR_variant	7/7	ENST00000555567.6	NP_002623.2
PGF	NM_001293643.1	c.*620A>G		3_prime_UTR_variant	7/7		NP_001280572.1
PGF	NM_001207012.1	c.*620A>G		3_prime_UTR_variant	6/6		NP_001193941.1
PGF	XM_047431476.1	c.*620A>G		3_prime_UTR_variant	6/6		XP_047287432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGF	ENST00000555567.6	c.*620A>G		3_prime_UTR_variant	7/7	1	NM_002632.6	ENSP00000451040.1
PGF	ENST00000553716.5	c.*620A>G		3_prime_UTR_variant	6/6	1		ENSP00000451413.1
PGF	ENST00000238607.10	c.*620A>G		3_prime_UTR_variant	7/7	3		ENSP00000238607.6

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31045 AN: 152022 Hom.: 3483 Cov.: 33

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.0963

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.184

GnomAD4 exome AF: 0.143 AC: 134 AN: 936 Hom.: 16 Cov.: 0 AF XY: 0.132 AC XY: 78 AN XY: 590

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.333

Gnomad4 EAS exome AF: 0.100

Gnomad4 SAS exome AF: 0.267

Gnomad4 FIN exome AF: 0.238

Gnomad4 NFE exome AF: 0.127

Gnomad4 OTH exome AF: 0.0400

GnomAD4 genome AF: 0.204 AC: 31098 AN: 152140 Hom.: 3496 Cov.: 33 AF XY: 0.208 AC XY: 15500 AN XY: 74384

Gnomad4 AFR AF: 0.283

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.0963

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.181

Alfa AF: 0.167 Hom.: 2273

Bravo AF: 0.200

Asia WGS AF: 0.208 AC: 726 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.8
DANN	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs8185; hg19: chr14-75408789;