chr14-74942340-T-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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	ENST00000555567.6	c.*366A>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_002632.6	ENSP00000451040.1
PGF	ENST00000553716.5	c.*366A>T		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000451413.1
PGF	ENST00000238607.10	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

African (AFR) AF: 0.448 AC: 535 AN: 1194

American (AMR) AF: 0.747 AC: 1071 AN: 1434

Ashkenazi Jewish (ASJ) AF: 0.874 AC: 1817 AN: 2078

East Asian (EAS) AF: 0.830 AC: 1689 AN: 2034

South Asian (SAS) AF: 0.693 AC: 8790 AN: 12688

European-Finnish (FIN) AF: 0.751 AC: 3084 AN: 4108

Middle Eastern (MID) AF: 0.800 AC: 272 AN: 340

European-Non Finnish (NFE) AF: 0.805 AC: 40038 AN: 49754

Other (OTH) AF: 0.789 AC: 3631 AN: 4604

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

African (AFR) AF: 0.444 AC: 18403 AN: 41456

American (AMR) AF: 0.778 AC: 11905 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.876 AC: 3039 AN: 3470

East Asian (EAS) AF: 0.852 AC: 4362 AN: 5122

South Asian (SAS) AF: 0.693 AC: 3339 AN: 4816

European-Finnish (FIN) AF: 0.741 AC: 7849 AN: 10586

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.804 AC: 54651 AN: 67964

Other (OTH) AF: 0.737 AC: 1557 AN: 2112

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
PhyloP100		0.064
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12411; hg19: chr14-75409043;