rs2007686

Variant names:

• chr1-91696886-C-T
• rs2007686
• NM_003243.5:c.2330-1107G>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.2330-1107G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,006 control chromosomes in the GnomAD database, including 3,566 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 0.21 (3566 hom., cov: 32)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.191
• Publications: 3 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.2330-1107G>A		intron_variant	Intron 15 of 16	ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9	c.2330-1107G>A		intron_variant	Intron 15 of 16	1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31441 AN: 151888 Hom.: 3562 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.0355

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.207 AC: 31454 AN: 152006 Hom.: 3566 Cov.: 32 AF XY: 0.205 AC XY: 15219 AN XY: 74292

African (AFR) AF: 0.149 AC: 6178 AN: 41450

American (AMR) AF: 0.268 AC: 4091 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 929 AN: 3468

East Asian (EAS) AF: 0.0359 AC: 186 AN: 5174

South Asian (SAS) AF: 0.301 AC: 1447 AN: 4808

European-Finnish (FIN) AF: 0.148 AC: 1563 AN: 10556

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16331 AN: 67966

Other (OTH) AF: 0.224 AC: 472 AN: 2110

Alfa AF: 0.219 Hom.: 859

Bravo AF: 0.212

Asia WGS AF: 0.163 AC: 570 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.55
PhyloP100		-0.19
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: rs2007686; hg19: chr1-92162443;