rs2391068

Variant names:

• chr1-91784928-C-T
• rs2391068
• NM_003243.5:c.246+12359G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003243.5(TGFBR3):​c.246+12359G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,174 control chromosomes in the GnomAD database, including 2,995 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 0.17 (2995 hom., cov: 32)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.103
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.246+12359G>A		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.246+12359G>A		intron_variant	Intron 3 of 16	1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25100 AN: 152056 Hom.: 2984 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.0585

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.0933

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.0925

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.165 AC: 25147 AN: 152174 Hom.: 2995 Cov.: 32 AF XY: 0.165 AC XY: 12277 AN XY: 74410

African (AFR) AF: 0.328 AC: 13599 AN: 41494

American (AMR) AF: 0.110 AC: 1680 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0585 AC: 203 AN: 3470

East Asian (EAS) AF: 0.249 AC: 1288 AN: 5166

South Asian (SAS) AF: 0.151 AC: 727 AN: 4824

European-Finnish (FIN) AF: 0.0933 AC: 990 AN: 10612

Middle Eastern (MID) AF: 0.137 AC: 40 AN: 292

European-Non Finnish (NFE) AF: 0.0925 AC: 6291 AN: 68002

Other (OTH) AF: 0.149 AC: 314 AN: 2108

Alfa AF: 0.116 Hom.: 308

Bravo AF: 0.172

Asia WGS AF: 0.219 AC: 765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.5
DANN	Benign	0.20
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2391068; hg19: chr1-92250485;