rs17881268

Positions:

• chr1-91797522-G-A
• chr1-91797522-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_003243.5(TGFBR3):​c.62-51C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0262 in 1,607,956 control chromosomes in the GnomAD database, including 688 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 0.018 (36 hom., cov: 33)
  • Exomes 𝑓: 0.027 (652 hom.)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260

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=-0.82).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0176 (2675/152342) while in subpopulation NFE AF= 0.0298 (2025/68038). AF 95% confidence interval is 0.0287. There are 36 homozygotes in gnomad4. There are 1222 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2675 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFBR3	NM_003243.5	c.62-51C>T		intron_variant		ENST00000212355.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFBR3	ENST00000212355.9	c.62-51C>T		intron_variant		1	NM_003243.5	P3

Frequencies

GnomAD3 genomes AF: 0.0176 AC: 2677 AN: 152224 Hom.: 36 Cov.: 33

Gnomad AFR AF: 0.00526

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00700

Gnomad ASJ AF: 0.00518

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0197

Gnomad FIN AF: 0.0173

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0298

Gnomad OTH AF: 0.0120

GnomAD3 exomes AF: 0.0183 AC: 4523 AN: 246576 Hom.: 62 AF XY: 0.0192 AC XY: 2581 AN XY: 134300

Gnomad AFR exome AF: 0.00487

Gnomad AMR exome AF: 0.00677

Gnomad ASJ exome AF: 0.00714

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0183

Gnomad FIN exome AF: 0.0179

Gnomad NFE exome AF: 0.0279

Gnomad OTH exome AF: 0.0187

GnomAD4 exome AF: 0.0271 AC: 39406 AN: 1455614 Hom.: 652 Cov.: 31 AF XY: 0.0267 AC XY: 19323 AN XY: 724560

Gnomad4 AFR exome AF: 0.00513

Gnomad4 AMR exome AF: 0.00687

Gnomad4 ASJ exome AF: 0.00797

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.0188

Gnomad4 FIN exome AF: 0.0174

Gnomad4 NFE exome AF: 0.0314

Gnomad4 OTH exome AF: 0.0221

GnomAD4 genome AF: 0.0176 AC: 2675 AN: 152342 Hom.: 36 Cov.: 33 AF XY: 0.0164 AC XY: 1222 AN XY: 74494

Gnomad4 AFR AF: 0.00527

Gnomad4 AMR AF: 0.00699

Gnomad4 ASJ AF: 0.00518

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0191

Gnomad4 FIN AF: 0.0173

Gnomad4 NFE AF: 0.0298

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.0244 Hom.: 13

Bravo AF: 0.0160

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.91
DANN	Benign	0.44

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: rs17881268; hg19: chr1-92263079;