rs17576372

Positions:

• chr1-91900617-T-C

Variant summary

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

The ENST00000370399.6(TGFBR3):​c.-174-920A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 152,174 control chromosomes in the GnomAD database, including 9,441 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 0.33 (9441 hom., cov: 33)
• Consequence: TGFBR3 ENST00000370399.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.107

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=-0.73).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFBR3	NM_001195684.1	c.-174-920A>G		intron_variant
TGFBR3	XM_047429247.1	c.-174-920A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFBR3	ENST00000370399.6	c.-174-920A>G		intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 50056 AN: 152056 Hom.: 9438 Cov.: 33

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.342

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.329 AC: 50062 AN: 152174 Hom.: 9441 Cov.: 33 AF XY: 0.333 AC XY: 24801 AN XY: 74378

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.435

Gnomad4 ASJ AF: 0.430

Gnomad4 EAS AF: 0.211

Gnomad4 SAS AF: 0.352

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.339

Alfa AF: 0.390 Hom.: 17545

Bravo AF: 0.321

Asia WGS AF: 0.326 AC: 1131 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	9.1
DANN	Benign	0.94

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17576372; hg19: chr1-92366174;