rs7532589

Variant names:

• chr1-91727122-G-T
• rs7532589
• NM_003243.5:c.885+537C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.885+537C>A		intron_variant	Intron 7 of 16	ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9	c.885+537C>A		intron_variant	Intron 7 of 16	1	NM_003243.5	ENSP00000212355.4

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

African (AFR) AF: 0.142 AC: 5875 AN: 41506

American (AMR) AF: 0.163 AC: 2490 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 572 AN: 3472

East Asian (EAS) AF: 0.0569 AC: 294 AN: 5168

South Asian (SAS) AF: 0.131 AC: 632 AN: 4824

European-Finnish (FIN) AF: 0.279 AC: 2941 AN: 10558

Middle Eastern (MID) AF: 0.229 AC: 67 AN: 292

European-Non Finnish (NFE) AF: 0.265 AC: 18015 AN: 67994

Other (OTH) AF: 0.218 AC: 461 AN: 2110

Alfa AF: 0.235 Hom.: 7289

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
PhyloP100		0.85
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: rs7532589; hg19: chr1-92192679;