rs17575497

Positions:

• chr1-91850339-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.61+11132G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 152,244 control chromosomes in the GnomAD database, including 19 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 0.010 (19 hom., cov: 31)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28

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=-0.8).
• BS2: High AC in GnomAd4 at 1581 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFBR3	NM_003243.5	c.61+11132G>A		intron_variant		ENST00000212355.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFBR3	ENST00000212355.9	c.61+11132G>A		intron_variant		1	NM_003243.5	P3

Frequencies

GnomAD3 genomes AF: 0.0104 AC: 1581 AN: 152126 Hom.: 19 Cov.: 31

Gnomad AFR AF: 0.00220

Gnomad AMI AF: 0.00879

Gnomad AMR AF: 0.0103

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0361

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0135

Gnomad OTH AF: 0.00621

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

GnomAD4 genome AF: 0.0104 AC: 1581 AN: 152244 Hom.: 19 Cov.: 31 AF XY: 0.0110 AC XY: 820 AN XY: 74434

Gnomad4 AFR AF: 0.00219

Gnomad4 AMR AF: 0.0103

Gnomad4 ASJ AF: 0.00260

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0361

Gnomad4 NFE AF: 0.0135

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.0100 Hom.: 4

Bravo AF: 0.00847

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.5
DANN	Benign	0.60

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: rs17575497; hg19: chr1-92315896;