Genetic Variant PGF:c.*366A>T (chr14-74942340-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0640

Publications

12 publications found

Variant links:

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]

PGF links:

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ACMG classification

Classification was made for transcript

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	Effect	Exon rank	MANE	Protein	UniProt
PGF	NM_002632.6 link	c.*366A>T	3_prime_UTR_variant	Exon 7 of 7	ENST00000555567.6	NP_002623.2	P49763-3Q53XY6Q86TW6
PGF	NM_001293643.1 link	c.*366A>T	3_prime_UTR_variant	Exon 7 of 7		NP_001280572.1	G3XA84Q86TW6
PGF	NM_001207012.1 link	c.*366A>T	3_prime_UTR_variant	Exon 6 of 6		NP_001193941.1	P49763-2Q86TW6
PGF	XM_047431476.1 link	c.*366A>T	3_prime_UTR_variant	Exon 6 of 6		XP_047287432.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PGF	ENST00000555567.6 link	c.*366A>T	3_prime_UTR_variant	Exon 7 of 7	1	NM_002632.6	ENSP00000451040.1	P49763-3
PGF	ENST00000553716.5 link	c.*366A>T	3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000451413.1	P49763-2
PGF	ENST00000238607.10 link	c.*366A>T	3_prime_UTR_variant	Exon 7 of 7	3		ENSP00000238607.6	G3XA84
PGF	ENST00000557748.5 link	n.*154A>T	downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.698

AC:

106083

AN:

151914

Hom.:

39107

Cov.:

show subpopulations

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.:

AF XY:

0.771

AC XY:

32531

AN XY:

42178

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

661

1323

1984

2646

3307

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

188

282

376

470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.698

AC:

106099

AN:

152032

Hom.:

39103

Cov.:

AF XY:

0.699

AC XY:

51907

AN XY:

74300

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1425

2851

4276

5702

7127

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

812

1624

2436

3248

4060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.81

PhyloP100

0.064

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over