rs2296621

chr1-91698229-G-T

Variant summary

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

The NM_003243.5(TGFBR3):c.2288-99C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 1,001,802 control chromosomes in the GnomAD database, including 13,932 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 0.15 (1814 hom., cov: 32)
  • Exomes 𝑓: 0.16 (12118 hom.)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFBR3	NM_003243.5	c.2288-99C>A		intron_variant		ENST00000212355.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFBR3	ENST00000212355.9	c.2288-99C>A		intron_variant		1	NM_003243.5	P3

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22241 AN: 152002 Hom.: 1812 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.0679

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.143

GnomAD4 exome AF: 0.164 AC: 139032 AN: 849682 Hom.: 12118 AF XY: 0.164 AC XY: 73227 AN XY: 447478

Gnomad4 AFR exome AF: 0.0991

Gnomad4 AMR exome AF: 0.0762

Gnomad4 ASJ exome AF: 0.112

Gnomad4 EAS exome AF: 0.0795

Gnomad4 SAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.178

Gnomad4 NFE exome AF: 0.184

Gnomad4 OTH exome AF: 0.156

GnomAD4 genome AF: 0.146 AC: 22257 AN: 152120 Hom.: 1814 Cov.: 32 AF XY: 0.144 AC XY: 10723 AN XY: 74362

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.0679

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.143

Alfa AF: 0.174 Hom.: 1140

Bravo AF: 0.141

Asia WGS AF: 0.0910 AC: 315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	12
Dann	Benign	0.71

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: rs2296621; hg19: chr1-92163786;