1-91861569-C-T

Variant names:

• chr1-91861569-C-T
• rs1805109
• NM_003243.5:c.-38G>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.-38G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,524,980 control chromosomes in the GnomAD database, including 11,178 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 0.12 (1534 hom., cov: 32)
  • Exomes 𝑓: 0.10 (9644 hom.)
• Consequence: TGFBR3 NM_003243.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.643
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.383 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.-38G>A		5_prime_UTR	Exon 2 of 17	NP_003234.2
	TGFBR3	NM_001195683.2		c.-38G>A		5_prime_UTR	Exon 2 of 17	NP_001182612.1
	TGFBR3	NM_001195684.1		c.-38G>A		5_prime_UTR	Exon 3 of 18	NP_001182613.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBR3	ENST00000212355.9	TSL:1 MANE Select	c.-38G>A		5_prime_UTR	Exon 2 of 17	ENSP00000212355.4
	TGFBR3	ENST00000525962.5	TSL:1	c.-38G>A		5_prime_UTR	Exon 1 of 16	ENSP00000436127.1
	TGFBR3	ENST00000370399.6	TSL:1	c.-38G>A		5_prime_UTR	Exon 3 of 18	ENSP00000359426.2

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18937 AN: 152084 Hom.: 1526 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.0934

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0842

Gnomad OTH AF: 0.117

GnomAD2 exomes AF: 0.130 AC: 32576 AN: 251020 AF XY: 0.128

Gnomad AFR exome AF: 0.165

Gnomad AMR exome AF: 0.125

Gnomad ASJ exome AF: 0.132

Gnomad EAS exome AF: 0.397

Gnomad FIN exome AF: 0.112

Gnomad NFE exome AF: 0.0854

Gnomad OTH exome AF: 0.109

GnomAD4 exome AF: 0.103 AC: 141032 AN: 1372778 Hom.: 9644 Cov.: 22 AF XY: 0.103 AC XY: 71028 AN XY: 688198

African (AFR) AF: 0.165 AC: 5250 AN: 31774

American (AMR) AF: 0.127 AC: 5673 AN: 44608

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 3474 AN: 25586

East Asian (EAS) AF: 0.418 AC: 16427 AN: 39292

South Asian (SAS) AF: 0.136 AC: 11463 AN: 84522

European-Finnish (FIN) AF: 0.110 AC: 5846 AN: 53322

Middle Eastern (MID) AF: 0.0770 AC: 430 AN: 5586

European-Non Finnish (NFE) AF: 0.0835 AC: 86025 AN: 1030584

Other (OTH) AF: 0.112 AC: 6444 AN: 57504

GnomAD4 genome AF: 0.125 AC: 18962 AN: 152202 Hom.: 1534 Cov.: 32 AF XY: 0.126 AC XY: 9394 AN XY: 74400

African (AFR) AF: 0.161 AC: 6699 AN: 41512

American (AMR) AF: 0.118 AC: 1808 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 463 AN: 3470

East Asian (EAS) AF: 0.397 AC: 2052 AN: 5168

South Asian (SAS) AF: 0.140 AC: 672 AN: 4816

European-Finnish (FIN) AF: 0.110 AC: 1168 AN: 10586

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0842 AC: 5729 AN: 68036

Other (OTH) AF: 0.123 AC: 260 AN: 2114

Alfa AF: 0.0983 Hom.: 1088

Bravo AF: 0.129

Asia WGS AF: 0.233 AC: 808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.6
DANN	Benign	0.64
PhyloP100		0.64
PromoterAI		-0.047	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	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: rs1805109; hg19: chr1-92327126; COSMIC: COSV53028786; COSMIC: COSV53028786;