NM_002632.6:c.*642C>G

Variant names:

• chr14-74942064-G-C
• rs1042886
• NM_002632.6:c.*642C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.197
• Publications: 9 publications found

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]

ACMG classification

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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGF	NM_002632.6	MANE Select	c.*642C>G		3_prime_UTR	Exon 7 of 7	NP_002623.2
	PGF	NM_001293643.1		c.*642C>G		3_prime_UTR	Exon 7 of 7	NP_001280572.1
	PGF	NM_001207012.1		c.*642C>G		3_prime_UTR	Exon 6 of 6	NP_001193941.1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.0173 AC: 2628 AN: 152096 Hom.: 56 Cov.: 33

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: 4 AN: 970 Hom.: 0 Cov.: 0 AF XY: 0.00464 AC XY: 3 AN XY: 646

African (AFR) AF: 0.00 AC: 0 AN: 10

American (AMR) AF: 0.100 AC: 1 AN: 10

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10

East Asian (EAS) AF: 0.00 AC: 0 AN: 14

South Asian (SAS) AF: 0.00 AC: 0 AN: 90

European-Finnish (FIN) AF: 0.0161 AC: 1 AN: 62

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.00276 AC: 2 AN: 724

Other (OTH) AF: 0.00 AC: 0 AN: 46

GnomAD4 genome AF: 0.0173 AC: 2639 AN: 152214 Hom.: 57 Cov.: 33 AF XY: 0.0173 AC XY: 1287 AN XY: 74410

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: 7 AN: 3468

East Asian (EAS) AF: 0.00657 AC: 34 AN: 5176

South Asian (SAS) AF: 0.0315 AC: 152 AN: 4826

European-Finnish (FIN) AF: 0.00236 AC: 25 AN: 10594

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00837 AC: 569 AN: 68004

Other (OTH) AF: 0.0142 AC: 30 AN: 2108

Alfa AF: 0.000577 Hom.: 495

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.34
DANN	Benign	0.51
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1042886; hg19: chr14-75408767;