Genetic Variant PGF:c.-230G>A (chr14-74955472-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.-230G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 388,668 control chromosomes in the GnomAD database, including 172 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 0.023 ( 146 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 26 hom. )

Consequence

PGF
NM_002632.6 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.255

Publications

4 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:

ENSG00000297555 (HGNC:):

ENSG00000297555 links:

Genome browser will be placed here

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=-0.69).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PGF	NM_002632.6 link	c.-230G>A	5_prime_UTR_variant	Exon 1 of 7	ENST00000555567.6	NP_002623.2	P49763-3Q53XY6Q86TW6
PGF	NM_001293643.1 link	c.-230G>A	5_prime_UTR_variant	Exon 1 of 7		NP_001280572.1	G3XA84Q86TW6
PGF	NM_001207012.1 link	c.-230G>A	5_prime_UTR_variant	Exon 1 of 6		NP_001193941.1	P49763-2Q86TW6
PGF	XM_047431476.1 link	c.-230G>A	5_prime_UTR_variant	Exon 1 of 6		XP_047287432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGF	ENST00000555567.6 link	c.-230G>A		5_prime_UTR_variant	Exon 1 of 7	1	NM_002632.6	ENSP00000451040.1		P49763-3

Frequencies

GnomAD3 genomes

AF:

0.0227

AC:

3449

AN:

152096

Hom.:

146

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0791

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00844

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000177

Gnomad OTH

AF:

0.0134

GnomAD4 exome

AF:

0.00292

AC:

690

AN:

236458

Hom.:

Cov.:

AF XY:

0.00242

AC XY:

292

AN XY:

120428

show subpopulations

African (AFR)

AF:

0.0787

AC:

539

AN:

6848

American (AMR)

AF:

0.00561

AC:

AN:

6950

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8894

East Asian (EAS)

AF:

0.00

AC:

AN:

22040

South Asian (SAS)

AF:

0.00

AC:

AN:

3330

European-Finnish (FIN)

AF:

0.00

AC:

AN:

19890

Middle Eastern (MID)

AF:

0.00162

AC:

AN:

1232

European-Non Finnish (NFE)

AF:

0.000106

AC:

AN:

151606

Other (OTH)

AF:

0.00600

AC:

AN:

15668

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

110

138

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0227

AC:

3454

AN:

152210

Hom.:

146

Cov.:

AF XY:

0.0210

AC XY:

1560

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0790

AC:

3282

AN:

41528

American (AMR)

AF:

0.00843

AC:

129

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000177

AC:

AN:

67976

Other (OTH)

AF:

0.0133

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

162

324

485

647

809

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:

0.0169

Hom.:

Bravo

AF:

0.0259

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

0.26

PromoterAI

0.059

Neutral

(source)

Mutation Taster

=300/0

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