NM_002608.4:c.64-1041G>C

Variant names:

• chr22-39236915-C-G
• rs5757572
• NM_002608.4:c.64-1041G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002608.4(PDGFB):​c.64-1041G>C 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 152,116 control chromosomes in the GnomAD database, including 27,532 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 (27532 hom., cov: 32)
• Consequence: PDGFB NM_002608.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.479
• Publications: 6 publications found

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]

PDGFB Gene-Disease associations (from GenCC):

• basal ganglia calcification, idiopathic, 5

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• bilateral striopallidodentate calcinosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial meningioma

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFB	NM_002608.4	c.64-1041G>C		intron_variant	Intron 1 of 6	ENST00000331163.11	NP_002599.1
PDGFB	NM_033016.3	c.19-1041G>C		intron_variant	Intron 1 of 6		NP_148937.1
PDGFB	XM_047441393.1	c.-30-1041G>C		intron_variant	Intron 1 of 6		XP_047297349.1
PDGFB	XM_047441394.1	c.-30-1041G>C		intron_variant	Intron 1 of 6		XP_047297350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDGFB	ENST00000331163.11	c.64-1041G>C		intron_variant	Intron 1 of 6	1	NM_002608.4	ENSP00000330382.6
PDGFB	ENST00000381551.8	c.19-1041G>C		intron_variant	Intron 1 of 6	5		ENSP00000370963.4
PDGFB	ENST00000455790.5	c.-30-1041G>C		intron_variant	Intron 1 of 4	4		ENSP00000402306.1
PDGFB	ENST00000440375.1	c.-30-1041G>C		intron_variant	Intron 1 of 4	4		ENSP00000405780.1

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88746 AN: 151998 Hom.: 27531 Cov.: 32

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.717

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.899

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.600

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

GnomAD4 genome AF: 0.584 AC: 88777 AN: 152116 Hom.: 27532 Cov.: 32 AF XY: 0.591 AC XY: 43929 AN XY: 74362

African (AFR) AF: 0.378 AC: 15677 AN: 41526

American (AMR) AF: 0.717 AC: 10955 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2388 AN: 3472

East Asian (EAS) AF: 0.898 AC: 4637 AN: 5162

South Asian (SAS) AF: 0.738 AC: 3548 AN: 4808

European-Finnish (FIN) AF: 0.625 AC: 6613 AN: 10582

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.633 AC: 43055 AN: 67980

Other (OTH) AF: 0.600 AC: 1268 AN: 2112

Alfa AF: 0.486 Hom.: 1455

Bravo AF: 0.582

Asia WGS AF: 0.790 AC: 2745 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.6
DANN	Benign	0.38
PhyloP100		0.48
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5757572; hg19: chr22-39632920;