1-91708858-G-A

Position:

• chr1-91708858-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003243.5(TGFBR3):​c.2167-75C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,582,730 control chromosomes in the GnomAD database, including 15,541 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 0.16 (2285 hom., cov: 32)
  • Exomes 𝑓: 0.12 (13256 hom.)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.973

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.2167-75C>T		intron_variant		ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9	c.2167-75C>T		intron_variant		1	NM_003243.5	ENSP00000212355	P3

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24014 AN: 152040 Hom.: 2271 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.0429

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.144

GnomAD4 exome AF: 0.123 AC: 175423 AN: 1430572 Hom.: 13256 AF XY: 0.121 AC XY: 85852 AN XY: 709942

Gnomad4 AFR exome AF: 0.215

Gnomad4 AMR exome AF: 0.192

Gnomad4 ASJ exome AF: 0.0451

Gnomad4 EAS exome AF: 0.418

Gnomad4 SAS exome AF: 0.0971

Gnomad4 FIN exome AF: 0.196

Gnomad4 NFE exome AF: 0.107

Gnomad4 OTH exome AF: 0.134

GnomAD4 genome AF: 0.158 AC: 24057 AN: 152158 Hom.: 2285 Cov.: 32 AF XY: 0.163 AC XY: 12161 AN XY: 74392

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.0429

Gnomad4 EAS AF: 0.391

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.146

Alfa AF: 0.113 Hom.: 1083

Bravo AF: 0.159

Asia WGS AF: 0.261 AC: 905 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	17
DANN	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs2038931; hg19: chr1-92174415; COSMIC: COSV53028691;