rs7532589

chr1-91727122-G-T

Variant summary

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

The NM_003243.5(TGFBR3):c.885+537C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,118 control chromosomes in the GnomAD database, including 3,689 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 0.21 (3689 hom., cov: 33)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.851

Genes affected

TGFBR3 (HGNC:11774): (transforming growth factor beta receptor 3) This locus encodes the transforming growth factor (TGF)-beta type III receptor. The encoded receptor is a membrane proteoglycan that often functions as a co-receptor with other TGF-beta receptor superfamily members. Ectodomain shedding produces soluble TGFBR3, which may inhibit TGFB signaling. Decreased expression of this receptor has been observed in various cancers. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene.[provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFBR3	NM_003243.5	c.885+537C>A		intron_variant		ENST00000212355.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFBR3	ENST00000212355.9	c.885+537C>A		intron_variant		1	NM_003243.5	P3

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31652 AN: 152000 Hom.: 3688 Cov.: 33

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.0569

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.208 AC: 31663 AN: 152118 Hom.: 3689 Cov.: 33 AF XY: 0.206 AC XY: 15289 AN XY: 74350

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.0569

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.218

Alfa AF: 0.217 Hom.: 552

Bravo AF: 0.201

Asia WGS AF: 0.0940 AC: 327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	7.6
Dann	Benign	0.79

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: rs7532589; hg19: chr1-92192679;