Genetic Variant PGF:c.315+60G>A (chr14-74949297-C-T) – 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.315+60G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 1,332,278 control chromosomes in the GnomAD database, including 110,132 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 0.34 ( 10192 hom., cov: 32)

Exomes 𝑓: 0.41 ( 99940 hom. )

Consequence

PGF
NM_002632.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.376

Publications

17 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:

LOC107984690 (HGNC:):

LOC107984690 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 (NFE) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002632.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PGF	NM_002632.6	MANE Select	c.315+60G>A	intron	N/A	NP_002623.2
PGF	NM_001293643.1		c.312+60G>A	intron	N/A	NP_001280572.1	Q86TW6
PGF	NM_001207012.1		c.315+60G>A	intron	N/A	NP_001193941.1	P49763-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PGF	ENST00000555567.6	TSL:1 MANE Select	c.315+60G>A	intron	N/A	ENSP00000451040.1	P49763-3
PGF	ENST00000553716.5	TSL:1	c.315+60G>A	intron	N/A	ENSP00000451413.1	P49763-2
PGF	ENST00000965660.1		c.315+60G>A	intron	N/A	ENSP00000635719.1

Frequencies

GnomAD3 genomes

AF:

0.344

AC:

52347

AN:

151952

Hom.:

10187

Cov.:

show subpopulations

Gnomad AFR

AF:

0.180

Gnomad AMI

AF:

0.432

Gnomad AMR

AF:

0.343

Gnomad ASJ

AF:

0.292

Gnomad EAS

AF:

0.238

Gnomad SAS

AF:

0.395

Gnomad FIN

AF:

0.577

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.414

Gnomad OTH

AF:

0.357

GnomAD4 exome

AF:

0.406

AC:

478677

AN:

1180208

Hom.:

99940

AF XY:

0.406

AC XY:

234853

AN XY:

578888

show subpopulations

African (AFR)

AF:

0.165

AC:

4215

AN:

25506

American (AMR)

AF:

0.285

AC:

6639

AN:

23304

Ashkenazi Jewish (ASJ)

AF:

0.296

AC:

5142

AN:

17360

East Asian (EAS)

AF:

0.248

AC:

7996

AN:

32256

South Asian (SAS)

AF:

0.399

AC:

21703

AN:

54390

European-Finnish (FIN)

AF:

0.566

AC:

26239

AN:

46384

Middle Eastern (MID)

AF:

0.301

AC:

1436

AN:

4774

European-Non Finnish (NFE)

AF:

0.417

AC:

387142

AN:

928160

Other (OTH)

AF:

0.378

AC:

18165

AN:

48074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

13737

27475

41212

54950

68687

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12384

24768

37152

49536

61920

<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:

0.344

AC:

52369

AN:

152070

Hom.:

10192

Cov.:

AF XY:

0.353

AC XY:

26253

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.180

AC:

7452

AN:

41472

American (AMR)

AF:

0.343

AC:

5241

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.292

AC:

1012

AN:

3468

East Asian (EAS)

AF:

0.238

AC:

1234

AN:

5178

South Asian (SAS)

AF:

0.395

AC:

1906

AN:

4826

European-Finnish (FIN)

AF:

0.577

AC:

6102

AN:

10572

Middle Eastern (MID)

AF:

0.356

AC:

104

AN:

292

European-Non Finnish (NFE)

AF:

0.414

AC:

28155

AN:

67948

Other (OTH)

AF:

0.365

AC:

771

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1645

3290

4934

6579

8224

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

512

1024

1536

2048

2560

<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:

0.373

Hom.:

16502

Bravo

AF:

0.317

Asia WGS

AF:

0.349

AC:

1212

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

7.5

(source)

DANN

Benign

0.74

PhyloP100

0.38

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over