chr14-74949297-C-T

Position:

• chr14-74949297-C-T

Variant summary

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

The ENST00000555567.6(PGF):​c.315+60G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 1,332,278 control chromosomes in the GnomAD database, including 110,132 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 0.34 (10192 hom., cov: 32)
  • Exomes 𝑓: 0.41 (99940 hom.)
• Consequence: PGF ENST00000555567.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.376

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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGF	NM_002632.6	c.315+60G>A		intron_variant		ENST00000555567.6	NP_002623.2
LOC107984690	XR_001750826.3	n.5465-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGF	ENST00000555567.6	c.315+60G>A		intron_variant		1	NM_002632.6	ENSP00000451040	P4

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52347 AN: 151952 Hom.: 10187 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.357

GnomAD4 exome AF: 0.406 AC: 478677 AN: 1180208 Hom.: 99940 AF XY: 0.406 AC XY: 234853 AN XY: 578888

Gnomad4 AFR exome AF: 0.165

Gnomad4 AMR exome AF: 0.285

Gnomad4 ASJ exome AF: 0.296

Gnomad4 EAS exome AF: 0.248

Gnomad4 SAS exome AF: 0.399

Gnomad4 FIN exome AF: 0.566

Gnomad4 NFE exome AF: 0.417

Gnomad4 OTH exome AF: 0.378

GnomAD4 genome AF: 0.344 AC: 52369 AN: 152070 Hom.: 10192 Cov.: 32 AF XY: 0.353 AC XY: 26253 AN XY: 74342

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.343

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.577

Gnomad4 NFE AF: 0.414

Gnomad4 OTH AF: 0.365

Alfa AF: 0.360 Hom.: 1811

Bravo AF: 0.317

Asia WGS AF: 0.349 AC: 1212 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.5
DANN	Benign	0.74

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

LitVar

Other links and lift over

dbSNP: rs2268614; hg19: chr14-75416000; COSMIC: COSV53126001; COSMIC: COSV53126001;