Genetic Variant PGF:c.*620A>G (chr14-74942086-T-C) – 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.*620A>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 0.204 in 153,076 control chromosomes in the GnomAD database, including 3,512 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 0.20 ( 3496 hom., cov: 33)

Exomes 𝑓: 0.14 ( 16 hom. )

Consequence

PGF
NM_002632.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0180

Publications

16 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 (AFR) allele frequency at 95% confidence interval = 0.279 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.*620A>G	3_prime_UTR	Exon 7 of 7	NP_002623.2
PGF	NM_001293643.1		c.*620A>G	3_prime_UTR	Exon 7 of 7	NP_001280572.1	Q86TW6
PGF	NM_001207012.1		c.*620A>G	3_prime_UTR	Exon 6 of 6	NP_001193941.1	P49763-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PGF	ENST00000555567.6	TSL:1 MANE Select	c.*620A>G	3_prime_UTR	Exon 7 of 7	ENSP00000451040.1	P49763-3
PGF	ENST00000553716.5	TSL:1	c.*620A>G	3_prime_UTR	Exon 6 of 6	ENSP00000451413.1	P49763-2
PGF	ENST00000965660.1		c.*620A>G	3_prime_UTR	Exon 8 of 8	ENSP00000635719.1

Frequencies

GnomAD3 genomes

AF:

0.204

AC:

31045

AN:

152022

Hom.:

3483

Cov.:

show subpopulations

Gnomad AFR

AF:

0.283

Gnomad AMI

AF:

0.155

Gnomad AMR

AF:

0.162

Gnomad ASJ

AF:

0.0963

Gnomad EAS

AF:

0.143

Gnomad SAS

AF:

0.261

Gnomad FIN

AF:

0.251

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.166

Gnomad OTH

AF:

0.184

GnomAD4 exome

AF:

0.143

AC:

134

AN:

936

Hom.:

Cov.:

AF XY:

0.132

AC XY:

AN XY:

590

show subpopulations

African (AFR)

AF:

0.125

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.333

AC:

AN:

East Asian (EAS)

AF:

0.100

AC:

AN:

South Asian (SAS)

AF:

0.267

AC:

AN:

European-Finnish (FIN)

AF:

0.238

AC:

AN:

Middle Eastern (MID)

AF:

0.750

AC:

AN:

European-Non Finnish (NFE)

AF:

0.127

AC:

AN:

716

Other (OTH)

AF:

0.0400

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

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:

0.204

AC:

31098

AN:

152140

Hom.:

3496

Cov.:

AF XY:

0.208

AC XY:

15500

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.283

AC:

11764

AN:

41496

American (AMR)

AF:

0.162

AC:

2473

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0963

AC:

334

AN:

3470

East Asian (EAS)

AF:

0.143

AC:

739

AN:

5172

South Asian (SAS)

AF:

0.262

AC:

1262

AN:

4824

European-Finnish (FIN)

AF:

0.251

AC:

2658

AN:

10584

Middle Eastern (MID)

AF:

0.150

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.166

AC:

11300

AN:

67984

Other (OTH)

AF:

0.181

AC:

383

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1244

2488

3733

4977

6221

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

322

644

966

1288

1610

<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:

0.169

Hom.:

2813

Bravo

AF:

0.200

Asia WGS

AF:

0.208

AC:

726

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.8

(source)

DANN

Benign

0.58

PhyloP100

-0.018

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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