Genetic Variant PGF:c.*642C>G (chr14-74942064-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_002632.6(PGF):c.*642C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0173 in 153,184 control chromosomes in the GnomAD database, including 57 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 0.017 ( 57 hom., cov: 33)

Exomes 𝑓: 0.0041 ( 0 hom. )

Consequence

PGF
NM_002632.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.197

Publications

9 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=-0.84).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0173 (2639/152214) while in subpopulation AFR AF = 0.0333 (1385/41536). AF 95% confidence interval is 0.0319. There are 57 homozygotes in GnomAd4. There are 1287 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 2639 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
PGF	NM_002632.6 link	c.*642C>G	3_prime_UTR_variant	Exon 7 of 7	ENST00000555567.6	NP_002623.2
PGF	NM_001293643.1 link	c.*642C>G	3_prime_UTR_variant	Exon 7 of 7		NP_001280572.1
PGF	NM_001207012.1 link	c.*642C>G	3_prime_UTR_variant	Exon 6 of 6		NP_001193941.1
PGF	XM_047431476.1 link	c.*642C>G	3_prime_UTR_variant	Exon 6 of 6		XP_047287432.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
PGF	ENST00000555567.6 link	c.*642C>G	3_prime_UTR_variant	Exon 7 of 7	1	NM_002632.6	ENSP00000451040.1
PGF	ENST00000553716.5 link	c.*642C>G	3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000451413.1
PGF	ENST00000238607.10 link	c.*642C>G	3_prime_UTR_variant	Exon 7 of 7	3		ENSP00000238607.6

Frequencies

GnomAD3 genomes

AF:

0.0173

AC:

2628

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0333

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0279

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00636

Gnomad SAS

AF:

0.0311

Gnomad FIN

AF:

0.00236

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00835

Gnomad OTH

AF:

0.0144

GnomAD4 exome

AF:

0.00412

AC:

AN:

970

Hom.:

Cov.:

AF XY:

0.00464

AC XY:

AN XY:

646

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.100

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.0161

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00276

AC:

AN:

724

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.613

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0173

AC:

2639

AN:

152214

Hom.:

Cov.:

AF XY:

0.0173

AC XY:

1287

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0333

AC:

1385

AN:

41536

American (AMR)

AF:

0.0280

AC:

428

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3468

East Asian (EAS)

AF:

0.00657

AC:

AN:

5176

South Asian (SAS)

AF:

0.0315

AC:

152

AN:

4826

European-Finnish (FIN)

AF:

0.00236

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00837

AC:

569

AN:

68004

Other (OTH)

AF:

0.0142

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

128

255

383

510

638

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<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:

0.000577

Hom.:

495

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.34

(source)

DANN

Benign

0.51

PhyloP100

-0.20

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over