rs284878

Variant names:

• chr1-91708703-A-G
• rs284878
• NM_003243.5:c.2247T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-91708703-A-G
• chr1-91708703-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_003243.5(TGFBR3):​c.2247T>C​(p.Thr749Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.938 in 1,614,092 control chromosomes in the GnomAD database, including 711,345 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.94 (66664 hom., cov: 31)
  • Exomes 𝑓: 0.94 (644681 hom.)
• Consequence: TGFBR3 NM_003243.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.68
• Publications: 26 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 1-91708703-A-G is Benign according to our data. Variant chr1-91708703-A-G is described in ClinVar as Benign. ClinVar VariationId is 3060406.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=2.68 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.935 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.2247T>C	p.Thr749Thr	synonymous	Exon 14 of 17	NP_003234.2	Q03167-1
	TGFBR3	NM_001195683.2		c.2244T>C	p.Thr748Thr	synonymous	Exon 14 of 17	NP_001182612.1	A0A0A8KWK3
	TGFBR3	NM_001195684.1		c.2244T>C	p.Thr748Thr	synonymous	Exon 15 of 18	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.2247T>C	p.Thr749Thr	synonymous	Exon 14 of 17	ENSP00000212355.4	Q03167-1
	TGFBR3	ENST00000525962.5	TSL:1	c.2247T>C	p.Thr749Thr	synonymous	Exon 13 of 16	ENSP00000436127.1	Q03167-1
	TGFBR3	ENST00000370399.6	TSL:1	c.2244T>C	p.Thr748Thr	synonymous	Exon 15 of 18	ENSP00000359426.2	Q03167-2

Frequencies

GnomAD3 genomes AF: 0.935 AC: 142250 AN: 152146 Hom.: 66606 Cov.: 31

Gnomad AFR AF: 0.936

Gnomad AMI AF: 0.938

Gnomad AMR AF: 0.944

Gnomad ASJ AF: 0.904

Gnomad EAS AF: 0.767

Gnomad SAS AF: 0.943

Gnomad FIN AF: 0.969

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.941

Gnomad OTH AF: 0.934

GnomAD2 exomes AF: 0.933 AC: 234439 AN: 251350 AF XY: 0.933

Gnomad AFR exome AF: 0.936

Gnomad AMR exome AF: 0.966

Gnomad ASJ exome AF: 0.904

Gnomad EAS exome AF: 0.762

Gnomad FIN exome AF: 0.970

Gnomad NFE exome AF: 0.941

Gnomad OTH exome AF: 0.945

GnomAD4 exome AF: 0.939 AC: 1372215 AN: 1461828 Hom.: 644681 Cov.: 66 AF XY: 0.939 AC XY: 682563 AN XY: 727216

African (AFR) AF: 0.934 AC: 31268 AN: 33476

American (AMR) AF: 0.963 AC: 43068 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.904 AC: 23636 AN: 26134

East Asian (EAS) AF: 0.805 AC: 31966 AN: 39696

South Asian (SAS) AF: 0.948 AC: 81750 AN: 86258

European-Finnish (FIN) AF: 0.969 AC: 51737 AN: 53416

Middle Eastern (MID) AF: 0.924 AC: 5330 AN: 5766

European-Non Finnish (NFE) AF: 0.942 AC: 1047002 AN: 1111972

Other (OTH) AF: 0.935 AC: 56458 AN: 60390

GnomAD4 genome AF: 0.935 AC: 142368 AN: 152264 Hom.: 66664 Cov.: 31 AF XY: 0.936 AC XY: 69670 AN XY: 74444

African (AFR) AF: 0.936 AC: 38894 AN: 41550

American (AMR) AF: 0.945 AC: 14444 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.904 AC: 3137 AN: 3472

East Asian (EAS) AF: 0.768 AC: 3976 AN: 5178

South Asian (SAS) AF: 0.943 AC: 4543 AN: 4820

European-Finnish (FIN) AF: 0.969 AC: 10283 AN: 10610

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.941 AC: 64002 AN: 68022

Other (OTH) AF: 0.931 AC: 1968 AN: 2114

Alfa AF: 0.937 Hom.: 278279

Bravo AF: 0.933

Asia WGS AF: 0.874 AC: 3040 AN: 3478

EpiCase AF: 0.938

EpiControl AF: 0.939

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	TGFBR3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	10
DANN	Benign	0.72
PhyloP100		2.7
Mutation Taster		=98/2	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: rs284878; hg19: chr1-92174260; COSMIC: COSV108027253;