rs17878444

Variant names:

• chr1-91772335-A-AATCCCATTTTTGTTTAGG
• rs17878444
• NM_003243.5:c.247-13603_247-13586dupCCTAAACAAAAATGGGAT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_003243.5(TGFBR3):​c.247-13603_247-13586dupCCTAAACAAAAATGGGAT variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (13640 hom., cov: 0)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.247-13603_247-13586dupCCTAAACAAAAATGGGAT		intron_variant	Intron 3 of 16	ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9	c.247-13586_247-13585insCCTAAACAAAAATGGGAT		intron_variant	Intron 3 of 16	1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62394 AN: 151218 Hom.: 13596 Cov.: 0

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.408

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

GnomAD4 genome AF: 0.413 AC: 62495 AN: 151338 Hom.: 13640 Cov.: 0 AF XY: 0.413 AC XY: 30522 AN XY: 73922

African (AFR) AF: 0.535 AC: 21991 AN: 41098

American (AMR) AF: 0.411 AC: 6263 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1356 AN: 3468

East Asian (EAS) AF: 0.129 AC: 665 AN: 5152

South Asian (SAS) AF: 0.474 AC: 2255 AN: 4756

European-Finnish (FIN) AF: 0.347 AC: 3639 AN: 10486

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.370 AC: 25075 AN: 67836

Other (OTH) AF: 0.406 AC: 855 AN: 2104

Alfa AF: 0.377 Hom.: 1030

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs17878444; hg19: chr1-92237892;