chr14-74950149-C-T

Position:

• chr14-74950149-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002632.6(PGF):​c.119-596G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0317 in 152,218 control chromosomes in the GnomAD database, including 276 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 0.032 (276 hom., cov: 32)
• Consequence: PGF NM_002632.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60

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]

LOC107984690 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGF	NM_002632.6	c.119-596G>A		intron_variant		ENST00000555567.6	NP_002623.2
LOC107984690	XR_001750826.3	n.6309C>T		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGF	ENST00000555567.6	c.119-596G>A		intron_variant		1	NM_002632.6	ENSP00000451040	P4

Frequencies

GnomAD3 genomes AF: 0.0316 AC: 4813 AN: 152100 Hom.: 276 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.0211

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0317 AC: 4818 AN: 152218 Hom.: 276 Cov.: 32 AF XY: 0.0294 AC XY: 2188 AN XY: 74434

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.0107

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.0209

Alfa AF: 0.0299 Hom.: 37

Bravo AF: 0.0360

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.7
DANN	Benign	0.88

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

LitVar

Other links and lift over

dbSNP: rs61759375; hg19: chr14-75416852;