1-91683720-C-T

Variant names:

• chr1-91683720-C-T
• rs1131243
• NM_003243.5:c.*19G>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.*19G>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 0.17 in 1,406,694 control chromosomes in the GnomAD database, including 19,366 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 0.14 (1601 hom., cov: 32)
  • Exomes 𝑓: 0.17 (17765 hom.)
• Consequence: TGFBR3 NM_003243.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.122
• Publications: 7 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=-0.49).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.172 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.*19G>A		3_prime_UTR	Exon 17 of 17	NP_003234.2	Q03167-1
	TGFBR3	NM_001195683.2		c.*19G>A		3_prime_UTR	Exon 17 of 17	NP_001182612.1	A0A0A8KWK3
	TGFBR3	NM_001195684.1		c.*19G>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.*19G>A		3_prime_UTR	Exon 17 of 17	ENSP00000212355.4	Q03167-1
	TGFBR3	ENST00000525962.5	TSL:1	c.*19G>A		3_prime_UTR	Exon 16 of 16	ENSP00000436127.1	Q03167-1
	TGFBR3	ENST00000370399.6	TSL:1	c.*19G>A		3_prime_UTR	Exon 18 of 18	ENSP00000359426.2	Q03167-2

Frequencies

GnomAD3 genomes AF: 0.143 AC: 20695 AN: 145188 Hom.: 1597 Cov.: 32

Gnomad AFR AF: 0.0907

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.163

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.128

GnomAD2 exomes AF: 0.135 AC: 20295 AN: 150396 AF XY: 0.136

Gnomad AFR exome AF: 0.0807

Gnomad AMR exome AF: 0.0920

Gnomad ASJ exome AF: 0.145

Gnomad EAS exome AF: 0.117

Gnomad FIN exome AF: 0.153

Gnomad NFE exome AF: 0.171

Gnomad OTH exome AF: 0.135

GnomAD4 exome AF: 0.173 AC: 218654 AN: 1261374 Hom.: 17765 Cov.: 31 AF XY: 0.173 AC XY: 107550 AN XY: 621954

African (AFR) AF: 0.0960 AC: 2651 AN: 27626

American (AMR) AF: 0.107 AC: 3472 AN: 32488

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 3678 AN: 20556

East Asian (EAS) AF: 0.161 AC: 4037 AN: 25074

South Asian (SAS) AF: 0.110 AC: 8544 AN: 77760

European-Finnish (FIN) AF: 0.226 AC: 5937 AN: 26262

Middle Eastern (MID) AF: 0.205 AC: 742 AN: 3622

European-Non Finnish (NFE) AF: 0.181 AC: 181194 AN: 998478

Other (OTH) AF: 0.170 AC: 8399 AN: 49508

GnomAD4 genome AF: 0.143 AC: 20713 AN: 145320 Hom.: 1601 Cov.: 32 AF XY: 0.142 AC XY: 10077 AN XY: 70826

African (AFR) AF: 0.0912 AC: 3667 AN: 40212

American (AMR) AF: 0.127 AC: 1861 AN: 14634

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 467 AN: 3372

East Asian (EAS) AF: 0.130 AC: 559 AN: 4316

South Asian (SAS) AF: 0.122 AC: 494 AN: 4056

European-Finnish (FIN) AF: 0.173 AC: 1641 AN: 9474

Middle Eastern (MID) AF: 0.162 AC: 47 AN: 290

European-Non Finnish (NFE) AF: 0.175 AC: 11527 AN: 66044

Other (OTH) AF: 0.127 AC: 261 AN: 2058

Alfa AF: 0.129 Hom.: 495

Bravo AF: 0.134

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	5.3
DANN	Benign	0.88
PhyloP100		-0.12
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1131243; hg19: chr1-92149277;