1-91682456-C-T

Variant names:

• chr1-91682456-C-T
• rs1804506
• NM_003243.5:c.*1283G>A

Variant summary

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

The NM_003243.5(TGFBR3):​c.*1283G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 439,832 control chromosomes in the GnomAD database, including 7,048 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 0.18 (2557 hom., cov: 25)
  • Exomes 𝑓: 0.16 (4491 hom.)
• Consequence: TGFBR3 NM_003243.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.227
• Publications: 23 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=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.427 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.*1283G>A		3_prime_UTR	Exon 17 of 17	NP_003234.2	Q03167-1
	TGFBR3	NM_001195683.2		c.*1283G>A		3_prime_UTR	Exon 17 of 17	NP_001182612.1	A0A0A8KWK3
	TGFBR3	NM_001195684.1		c.*1283G>A		3_prime_UTR	Exon 18 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.*1283G>A		3_prime_UTR	Exon 17 of 17	ENSP00000212355.4	Q03167-1
	TGFBR3	ENST00000525962.5	TSL:1	c.*1283G>A		3_prime_UTR	Exon 16 of 16	ENSP00000436127.1	Q03167-1
	TGFBR3	ENST00000370399.6	TSL:1	c.*1283G>A		3_prime_UTR	Exon 18 of 18	ENSP00000359426.2	Q03167-2

Frequencies

GnomAD3 genomes AF: 0.182 AC: 25189 AN: 138614 Hom.: 2553 Cov.: 25

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.0830

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.0940

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.194

GnomAD2 exomes AF: 0.180 AC: 23355 AN: 130108 AF XY: 0.170

Gnomad AFR exome AF: 0.182

Gnomad AMR exome AF: 0.249

Gnomad ASJ exome AF: 0.109

Gnomad EAS exome AF: 0.414

Gnomad FIN exome AF: 0.274

Gnomad NFE exome AF: 0.141

Gnomad OTH exome AF: 0.169

GnomAD4 exome AF: 0.156 AC: 46887 AN: 301160 Hom.: 4491 Cov.: 0 AF XY: 0.147 AC XY: 25231 AN XY: 171538

African (AFR) AF: 0.179 AC: 1531 AN: 8538

American (AMR) AF: 0.248 AC: 6743 AN: 27230

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 1169 AN: 10772

East Asian (EAS) AF: 0.426 AC: 3920 AN: 9206

South Asian (SAS) AF: 0.0861 AC: 5124 AN: 59514

European-Finnish (FIN) AF: 0.255 AC: 3148 AN: 12364

Middle Eastern (MID) AF: 0.102 AC: 117 AN: 1148

European-Non Finnish (NFE) AF: 0.144 AC: 22879 AN: 158380

Other (OTH) AF: 0.161 AC: 2256 AN: 14008

GnomAD4 genome AF: 0.182 AC: 25199 AN: 138672 Hom.: 2557 Cov.: 25 AF XY: 0.190 AC XY: 12612 AN XY: 66500

African (AFR) AF: 0.190 AC: 6902 AN: 36408

American (AMR) AF: 0.232 AC: 3076 AN: 13232

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 363 AN: 3408

East Asian (EAS) AF: 0.443 AC: 2133 AN: 4818

South Asian (SAS) AF: 0.0938 AC: 413 AN: 4404

European-Finnish (FIN) AF: 0.292 AC: 2248 AN: 7696

Middle Eastern (MID) AF: 0.149 AC: 34 AN: 228

European-Non Finnish (NFE) AF: 0.146 AC: 9583 AN: 65690

Other (OTH) AF: 0.197 AC: 373 AN: 1896

Alfa AF: 0.151 Hom.: 3534

Bravo AF: 0.178

Asia WGS AF: 0.257 AC: 895 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	8.7
DANN	Benign	0.61
PhyloP100		0.23
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: rs1804506; hg19: chr1-92148013;