rs10493859

Variant names:

• chr1-91808087-C-A
• rs10493859
• NM_003243.5:c.62-10616G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003243.5(TGFBR3):​c.62-10616G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,082 control chromosomes in the GnomAD database, including 5,648 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 0.24 (5648 hom., cov: 32)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.778
• Publications: 9 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.62-10616G>T		intron_variant	Intron 2 of 16	ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9	c.62-10616G>T		intron_variant	Intron 2 of 16	1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37226 AN: 151964 Hom.: 5644 Cov.: 32

Gnomad AFR AF: 0.0851

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.0374

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.245 AC: 37240 AN: 152082 Hom.: 5648 Cov.: 32 AF XY: 0.244 AC XY: 18100 AN XY: 74332

African (AFR) AF: 0.0849 AC: 3525 AN: 41532

American (AMR) AF: 0.326 AC: 4976 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1099 AN: 3470

East Asian (EAS) AF: 0.0373 AC: 193 AN: 5180

South Asian (SAS) AF: 0.334 AC: 1608 AN: 4812

European-Finnish (FIN) AF: 0.261 AC: 2751 AN: 10544

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.325 AC: 22120 AN: 67964

Other (OTH) AF: 0.275 AC: 580 AN: 2108

Alfa AF: 0.302 Hom.: 5712

Bravo AF: 0.242

Asia WGS AF: 0.180 AC: 624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	13
DANN	Benign	0.70
PhyloP100		0.78
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: rs10493859; hg19: chr1-92273644;