rs1131243

Positions:

• chr1-91683720-C-G
• chr1-91683720-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_003243.5(TGFBR3):​c.*19G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000182 in 1,261,744 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000089 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000018 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TGFBR3 NM_003243.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.122

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BS2: High AC in GnomAdExome4 at 23 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFBR3	NM_003243.5	c.*19G>C		3_prime_UTR_variant	17/17	ENST00000212355.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFBR3	ENST00000212355.9	c.*19G>C		3_prime_UTR_variant	17/17	1	NM_003243.5	P3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 13 AN: 145198 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.0000997

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000684

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000232

Gnomad SAS AF: 0.000495

Gnomad FIN AF: 0.000106

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000606

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000182 AC: 23 AN: 1261744 Hom.: 0 Cov.: 31 AF XY: 0.0000241 AC XY: 15 AN XY: 622120

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000798

Gnomad4 SAS exome AF: 0.0000129

Gnomad4 FIN exome AF: 0.0000761

Gnomad4 NFE exome AF: 0.0000170

Gnomad4 OTH exome AF: 0.0000202

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000895 AC: 13 AN: 145330 Hom.: 0 Cov.: 32 AF XY: 0.0000847 AC XY: 6 AN XY: 70826

Gnomad4 AFR AF: 0.0000995

Gnomad4 AMR AF: 0.0000683

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000232

Gnomad4 SAS AF: 0.000493

Gnomad4 FIN AF: 0.000106

Gnomad4 NFE AF: 0.0000606

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	3.3
DANN	Benign	0.65

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: rs1131243; hg19: chr1-92149277;