22-39237617-C-T

Position:

• chr22-39237617-C-T

Variant summary

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

The NM_002608.4(PDGFB):​c.64-1743G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 152,028 control chromosomes in the GnomAD database, including 27,588 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 0.58 (27588 hom., cov: 32)
• Consequence: PDGFB NM_002608.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.515

Genes affected

PDGFB (HGNC:8800): (platelet derived growth factor subunit B) This gene encodes a member of the protein family comprised of both platelet-derived growth factors (PDGF) and vascular endothelial growth factors (VEGF). The encoded preproprotein is proteolytically processed to generate platelet-derived growth factor subunit B, which can homodimerize, or alternatively, heterodimerize with the related platelet-derived growth factor subunit A. These proteins bind and activate PDGF receptor tyrosine kinases, which play a role in a wide range of developmental processes. Mutations in this gene are associated with meningioma. Reciprocal translocations between chromosomes 22 and 17, at sites where this gene and that for collagen type 1, alpha 1 are located, are associated with dermatofibrosarcoma protuberans, a rare skin tumor. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDGFB	NM_002608.4	c.64-1743G>A		intron_variant		ENST00000331163.11	NP_002599.1
PDGFB	NM_033016.3	c.19-1743G>A		intron_variant			NP_148937.1
PDGFB	XM_047441393.1	c.-30-1743G>A		intron_variant			XP_047297349.1
PDGFB	XM_047441394.1	c.-30-1743G>A		intron_variant			XP_047297350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDGFB	ENST00000331163.11	c.64-1743G>A		intron_variant		1	NM_002608.4	ENSP00000330382.6
PDGFB	ENST00000381551.8	c.19-1743G>A		intron_variant		5		ENSP00000370963.4
PDGFB	ENST00000455790.5	c.-30-1743G>A		intron_variant		4		ENSP00000402306.1
PDGFB	ENST00000440375.1	c.-30-1743G>A		intron_variant		4		ENSP00000405780.1

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88737 AN: 151910 Hom.: 27586 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.696

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.597

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

GnomAD4 genome AF: 0.584 AC: 88771 AN: 152028 Hom.: 27588 Cov.: 32 AF XY: 0.591 AC XY: 43914 AN XY: 74308

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.717

Gnomad4 ASJ AF: 0.696

Gnomad4 EAS AF: 0.900

Gnomad4 SAS AF: 0.736

Gnomad4 FIN AF: 0.624

Gnomad4 NFE AF: 0.635

Gnomad4 OTH AF: 0.598

Alfa AF: 0.630 Hom.: 41047

Bravo AF: 0.581

Asia WGS AF: 0.793 AC: 2757 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.6
DANN	Benign	0.82

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: rs5757573; hg19: chr22-39633622;