rs2291477

Positions:

• chr1-91712778-C-G

Variant summary

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

The NM_003243.5(TGFBR3):​c.1867-236G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,136 control chromosomes in the GnomAD database, including 2,134 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 0.16 (2134 hom., cov: 33)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.1867-236G>C		intron_variant		ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9	c.1867-236G>C		intron_variant		1	NM_003243.5	ENSP00000212355	P3

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24430 AN: 152018 Hom.: 2133 Cov.: 33

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.0673

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.161 AC: 24440 AN: 152136 Hom.: 2134 Cov.: 33 AF XY: 0.158 AC XY: 11726 AN XY: 74376

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.0672

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.150

Alfa AF: 0.179 Hom.: 285

Bravo AF: 0.156

Asia WGS AF: 0.101 AC: 350 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.44

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: rs2291477; hg19: chr1-92178335;