rs10874909

Variant names:

• chr1-91726826-A-G
• rs10874909
• NM_003243.5:c.885+833T>C

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+833T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0604 in 151,346 control chromosomes in the GnomAD database, including 377 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 0.060 (377 hom., cov: 32)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0140
• Publications: 4 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003243.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBR3	NM_003243.5	MANE Select	c.885+833T>C		intron	N/A	NP_003234.2	Q03167-1
	TGFBR3	NM_001195683.2		c.885+833T>C		intron	N/A	NP_001182612.1	A0A0A8KWK3
	TGFBR3	NM_001195684.1		c.885+833T>C		intron	N/A	NP_001182613.1	A0A0A8KWK3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBR3	ENST00000212355.9	TSL:1 MANE Select	c.885+833T>C		intron	N/A	ENSP00000212355.4	Q03167-1
	TGFBR3	ENST00000525962.5	TSL:1	c.885+833T>C		intron	N/A	ENSP00000436127.1	Q03167-1
	TGFBR3	ENST00000370399.6	TSL:1	c.885+833T>C		intron	N/A	ENSP00000359426.2	Q03167-2

Frequencies

GnomAD3 genomes AF: 0.0604 AC: 9142 AN: 151242 Hom.: 378 Cov.: 32

Gnomad AFR AF: 0.0471

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0501

Gnomad ASJ AF: 0.0863

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.0569

Gnomad FIN AF: 0.0437

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0599

Gnomad OTH AF: 0.0605

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

GnomAD4 genome AF: 0.0604 AC: 9136 AN: 151346 Hom.: 377 Cov.: 32 AF XY: 0.0599 AC XY: 4431 AN XY: 73938

African (AFR) AF: 0.0470 AC: 1940 AN: 41272

American (AMR) AF: 0.0500 AC: 760 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.0863 AC: 299 AN: 3466

East Asian (EAS) AF: 0.221 AC: 1135 AN: 5132

South Asian (SAS) AF: 0.0572 AC: 274 AN: 4792

European-Finnish (FIN) AF: 0.0437 AC: 449 AN: 10272

Middle Eastern (MID) AF: 0.0822 AC: 24 AN: 292

European-Non Finnish (NFE) AF: 0.0599 AC: 4071 AN: 67912

Other (OTH) AF: 0.0604 AC: 127 AN: 2104

Alfa AF: 0.0577 Hom.: 49

Bravo AF: 0.0609

Asia WGS AF: 0.118 AC: 409 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.87
DANN	Benign	0.63
PhyloP100		0.014
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: rs10874909; hg19: chr1-92192383;