rs284185

Variant names:

• chr1-91768263-T-A
• rs284185
• NM_003243.5:c.247-9513A>T

Your query was ambiguous. Multiple possible variants found:

• chr1-91768263-T-A
• chr1-91768263-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003243.5(TGFBR3):​c.247-9513A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 151,258 control chromosomes in the GnomAD database, including 23,061 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 0.55 (23061 hom., cov: 29)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.645
• Publications: 8 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.572 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.247-9513A>T		intron	N/A	NP_003234.2	Q03167-1
	TGFBR3	NM_001195683.2		c.247-9513A>T		intron	N/A	NP_001182612.1	A0A0A8KWK3
	TGFBR3	NM_001195684.1		c.247-9513A>T		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.247-9513A>T		intron	N/A	ENSP00000212355.4	Q03167-1
	TGFBR3	ENST00000525962.5	TSL:1	c.247-9513A>T		intron	N/A	ENSP00000436127.1	Q03167-1
	TGFBR3	ENST00000370399.6	TSL:1	c.247-9513A>T		intron	N/A	ENSP00000359426.2	Q03167-2

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82387 AN: 151142 Hom.: 23033 Cov.: 29

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.536

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.545 AC: 82461 AN: 151258 Hom.: 23061 Cov.: 29 AF XY: 0.545 AC XY: 40226 AN XY: 73826

African (AFR) AF: 0.532 AC: 21903 AN: 41158

American (AMR) AF: 0.527 AC: 8027 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.536 AC: 1857 AN: 3462

East Asian (EAS) AF: 0.122 AC: 629 AN: 5158

South Asian (SAS) AF: 0.579 AC: 2780 AN: 4802

European-Finnish (FIN) AF: 0.615 AC: 6292 AN: 10234

Middle Eastern (MID) AF: 0.592 AC: 173 AN: 292

European-Non Finnish (NFE) AF: 0.577 AC: 39164 AN: 67910

Other (OTH) AF: 0.529 AC: 1113 AN: 2102

Alfa AF: 0.418 Hom.: 1081

Bravo AF: 0.535

Asia WGS AF: 0.353 AC: 1231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.79
PhyloP100		-0.65
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: rs284185; hg19: chr1-92233820;