NM_003243.5:c.*457A>G

Variant names:

• chr1-91683282-T-C
• rs1805117
• NM_003243.5:c.*457A>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.*457A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 456,306 control chromosomes in the GnomAD database, including 4,979 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 0.13 (1535 hom., cov: 32)
  • Exomes 𝑓: 0.14 (3444 hom.)
• Consequence: TGFBR3 NM_003243.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.148
• Publications: 14 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.167 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBR3	NM_003243.5	MANE Select	c.*457A>G		3_prime_UTR	Exon 17 of 17	NP_003234.2
	TGFBR3	NM_001195683.2		c.*457A>G		3_prime_UTR	Exon 17 of 17	NP_001182612.1
	TGFBR3	NM_001195684.1		c.*457A>G		3_prime_UTR	Exon 18 of 18	NP_001182613.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBR3	ENST00000212355.9	TSL:1 MANE Select	c.*457A>G		3_prime_UTR	Exon 17 of 17	ENSP00000212355.4
	TGFBR3	ENST00000525962.5	TSL:1	c.*457A>G		3_prime_UTR	Exon 16 of 16	ENSP00000436127.1
	TGFBR3	ENST00000370399.6	TSL:1	c.*457A>G		3_prime_UTR	Exon 18 of 18	ENSP00000359426.2

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20196 AN: 152092 Hom.: 1536 Cov.: 32

Gnomad AFR AF: 0.0754

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.124

GnomAD2 exomes AF: 0.135 AC: 18493 AN: 136558 AF XY: 0.137

Gnomad AFR exome AF: 0.0716

Gnomad AMR exome AF: 0.0918

Gnomad ASJ exome AF: 0.145

Gnomad EAS exome AF: 0.120

Gnomad FIN exome AF: 0.158

Gnomad NFE exome AF: 0.173

Gnomad OTH exome AF: 0.133

GnomAD4 exome AF: 0.145 AC: 44067 AN: 304096 Hom.: 3444 Cov.: 0 AF XY: 0.143 AC XY: 24845 AN XY: 173192

African (AFR) AF: 0.0733 AC: 634 AN: 8646

American (AMR) AF: 0.0909 AC: 2483 AN: 27316

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 1589 AN: 10892

East Asian (EAS) AF: 0.114 AC: 1062 AN: 9280

South Asian (SAS) AF: 0.109 AC: 6521 AN: 59676

European-Finnish (FIN) AF: 0.165 AC: 2119 AN: 12850

Middle Eastern (MID) AF: 0.163 AC: 188 AN: 1156

European-Non Finnish (NFE) AF: 0.171 AC: 27415 AN: 160102

Other (OTH) AF: 0.145 AC: 2056 AN: 14178

GnomAD4 genome AF: 0.133 AC: 20193 AN: 152210 Hom.: 1535 Cov.: 32 AF XY: 0.132 AC XY: 9829 AN XY: 74418

African (AFR) AF: 0.0753 AC: 3129 AN: 41532

American (AMR) AF: 0.119 AC: 1819 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 467 AN: 3470

East Asian (EAS) AF: 0.109 AC: 566 AN: 5176

South Asian (SAS) AF: 0.106 AC: 509 AN: 4824

European-Finnish (FIN) AF: 0.156 AC: 1653 AN: 10604

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11557 AN: 67982

Other (OTH) AF: 0.122 AC: 259 AN: 2116

Alfa AF: 0.155 Hom.: 2683

Bravo AF: 0.130

Asia WGS AF: 0.0870 AC: 304 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	13
DANN	Benign	0.72
PhyloP100		0.15
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: rs1805117; hg19: chr1-92148839;