dbSNP rs2268613: PGF:c.*909C>T (chr14-74941797-G-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.*909C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 152,474 control chromosomes in the GnomAD database, including 38,986 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 0.69 ( 38848 hom., cov: 31)

Exomes 𝑓: 0.77 ( 138 hom. )

Consequence

PGF
NM_002632.6 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.17

Publications

15 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=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
PGF	NM_002632.6 link	c.*909C>T	downstream_gene_variant	ENST00000555567.6	NP_002623.2	P49763-3Q53XY6Q86TW6
PGF	NM_001293643.1 link	c.*909C>T	downstream_gene_variant		NP_001280572.1	G3XA84Q86TW6
PGF	NM_001207012.1 link	c.*909C>T	downstream_gene_variant		NP_001193941.1	P49763-2Q86TW6
PGF	XM_047431476.1 link	c.*909C>T	downstream_gene_variant		XP_047287432.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
PGF	ENST00000555567.6 link	c.*909C>T	downstream_gene_variant	1	NM_002632.6	ENSP00000451040.1	P49763-3
PGF	ENST00000553716.5 link	c.*909C>T	downstream_gene_variant	1		ENSP00000451413.1	P49763-2
PGF	ENST00000238607.10 link	c.*909C>T	downstream_gene_variant	3		ENSP00000238607.6	G3XA84

Frequencies

GnomAD3 genomes

AF:

0.695

AC:

105584

AN:

151888

Hom.:

38853

Cov.:

show subpopulations

Gnomad AFR

AF:

0.437

Gnomad AMI

AF:

0.836

Gnomad AMR

AF:

0.776

Gnomad ASJ

AF:

0.865

Gnomad EAS

AF:

0.851

Gnomad SAS

AF:

0.688

Gnomad FIN

AF:

0.742

Gnomad MID

AF:

0.794

Gnomad NFE

AF:

0.803

Gnomad OTH

AF:

0.729

GnomAD4 exome

AF:

0.769

AC:

360

AN:

468

Hom.:

138

Cov.:

AF XY:

0.774

AC XY:

223

AN XY:

288

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.756

AC:

325

AN:

430

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AF:

0.667

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<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:

0.695

AC:

105597

AN:

152006

Hom.:

38848

Cov.:

AF XY:

0.695

AC XY:

51658

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.436

AC:

18045

AN:

41416

American (AMR)

AF:

0.776

AC:

11855

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.865

AC:

3002

AN:

3470

East Asian (EAS)

AF:

0.851

AC:

4389

AN:

5156

South Asian (SAS)

AF:

0.688

AC:

3308

AN:

4810

European-Finnish (FIN)

AF:

0.742

AC:

7836

AN:

10560

Middle Eastern (MID)

AF:

0.776

AC:

228

AN:

294

European-Non Finnish (NFE)

AF:

0.803

AC:

54622

AN:

67996

Other (OTH)

AF:

0.733

AC:

1550

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1430

2861

4291

5722

7152

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

810

1620

2430

3240

4050

<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:

0.777

Hom.:

194753

Bravo

AF:

0.687

Asia WGS

AF:

0.742

AC:

2580

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.11

(source)

DANN

Benign

0.65

PhyloP100

-2.2

Mutation Taster

=94/6

polymorphism

(source)

Splicing

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