rs12411

Variant names:

• chr14-74942340-T-A
• rs12411
• NM_002632.6:c.*366A>T

Variant summary

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

The NM_002632.6(PGF):​c.*366A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.725 in 230,266 control chromosomes in the GnomAD database, including 63,137 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 0.70 (39103 hom., cov: 32)
  • Exomes 𝑓: 0.78 (24034 hom.)
• Consequence: PGF NM_002632.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGF	NM_002632.6	c.*366A>T		3_prime_UTR_variant	Exon 7 of 7	ENST00000555567.6	NP_002623.2
PGF	NM_001293643.1	c.*366A>T		3_prime_UTR_variant	Exon 7 of 7		NP_001280572.1
PGF	NM_001207012.1	c.*366A>T		3_prime_UTR_variant	Exon 6 of 6		NP_001193941.1
PGF	XM_047431476.1	c.*366A>T		3_prime_UTR_variant	Exon 6 of 6		XP_047287432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGF	ENST00000555567	c.*366A>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_002632.6	ENSP00000451040.1
PGF	ENST00000553716	c.*366A>T		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000451413.1
PGF	ENST00000238607	c.*366A>T		3_prime_UTR_variant	Exon 7 of 7	3		ENSP00000238607.6
PGF	ENST00000557748.5	n.*154A>T		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106083 AN: 151914 Hom.: 39107 Cov.: 32

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.836

Gnomad AMR AF: 0.778

Gnomad ASJ AF: 0.876

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.741

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.804

Gnomad OTH AF: 0.733

GnomAD4 exome AF: 0.779 AC: 60927 AN: 78234 Hom.: 24034 Cov.: 0 AF XY: 0.771 AC XY: 32531 AN XY: 42178

Gnomad4 AFR exome AF: 0.448

Gnomad4 AMR exome AF: 0.747

Gnomad4 ASJ exome AF: 0.874

Gnomad4 EAS exome AF: 0.830

Gnomad4 SAS exome AF: 0.693

Gnomad4 FIN exome AF: 0.751

Gnomad4 NFE exome AF: 0.805

Gnomad4 OTH exome AF: 0.789

GnomAD4 genome AF: 0.698 AC: 106099 AN: 152032 Hom.: 39103 Cov.: 32 AF XY: 0.699 AC XY: 51907 AN XY: 74300

Gnomad4 AFR AF: 0.444

Gnomad4 AMR AF: 0.778

Gnomad4 ASJ AF: 0.876

Gnomad4 EAS AF: 0.852

Gnomad4 SAS AF: 0.693

Gnomad4 FIN AF: 0.741

Gnomad4 NFE AF: 0.804

Gnomad4 OTH AF: 0.737

Alfa AF: 0.746 Hom.: 5456

Bravo AF: 0.691

Asia WGS AF: 0.745 AC: 2588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.1
DANN	Benign	0.81

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: rs12411; hg19: chr14-75409043;