Genetic Variant PGF:c.*642C>A (chr14-74942064-G-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.*642C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.09 in 153,160 control chromosomes in the GnomAD database, including 854 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 0.090 ( 850 hom., cov: 33)

Exomes 𝑓: 0.087 ( 4 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=-0.83).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.233 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
PGF	NM_002632.6	MANE Select	c.*642C>A	3_prime_UTR	Exon 7 of 7	NP_002623.2
PGF	NM_001293643.1		c.*642C>A	3_prime_UTR	Exon 7 of 7	NP_001280572.1
PGF	NM_001207012.1		c.*642C>A	3_prime_UTR	Exon 6 of 6	NP_001193941.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PGF	ENST00000555567.6	TSL:1 MANE Select	c.*642C>A	3_prime_UTR	Exon 7 of 7	ENSP00000451040.1
PGF	ENST00000553716.5	TSL:1	c.*642C>A	3_prime_UTR	Exon 6 of 6	ENSP00000451413.1
PGF	ENST00000238607.10	TSL:3	c.*642C>A	3_prime_UTR	Exon 7 of 7	ENSP00000238607.6

Frequencies

GnomAD3 genomes

AF:

0.0901

AC:

13707

AN:

152080

Hom.:

851

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0203

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.0981

Gnomad ASJ

AF:

0.0828

Gnomad EAS

AF:

0.140

Gnomad SAS

AF:

0.244

Gnomad FIN

AF:

0.194

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.0834

GnomAD4 exome

AF:

0.0873

AC:

AN:

962

Hom.:

Cov.:

AF XY:

0.0891

AC XY:

AN XY:

640

show subpopulations

African (AFR)

AF:

0.100

AC:

AN:

American (AMR)

AF:

0.100

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.0714

AC:

AN:

South Asian (SAS)

AF:

0.227

AC:

AN:

European-Finnish (FIN)

AF:

0.194

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0627

AC:

AN:

718

Other (OTH)

AF:

0.0870

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0901

AC:

13707

AN:

152198

Hom.:

850

Cov.:

AF XY:

0.0974

AC XY:

7246

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.0203

AC:

842

AN:

41530

American (AMR)

AF:

0.0983

AC:

1503

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0828

AC:

287

AN:

3468

East Asian (EAS)

AF:

0.140

AC:

724

AN:

5176

South Asian (SAS)

AF:

0.244

AC:

1179

AN:

4824

European-Finnish (FIN)

AF:

0.194

AC:

2055

AN:

10588

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.102

AC:

6905

AN:

68002

Other (OTH)

AF:

0.0821

AC:

173

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

635

1270

1906

2541

3176

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

344

516

688

860

<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:

0.0915

Hom.:

495

Bravo

AF:

0.0798

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.89

(source)

DANN

Benign

0.59

PhyloP100

-0.20

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