rs6700529

Variant names:

• chr1-91770785-C-A
• rs6700529
• NM_003243.5:c.247-12035G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-91770785-C-A
• chr1-91770785-C-G

Variant summary

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

The NM_003243.5(TGFBR3):​c.247-12035G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,112 control chromosomes in the GnomAD database, including 1,398 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 0.13 (1398 hom., cov: 32)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.247-12035G>T		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.247-12035G>T		intron_variant	Intron 3 of 16	1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19187 AN: 151988 Hom.: 1377 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0418

Gnomad SAS AF: 0.0724

Gnomad FIN AF: 0.0852

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.131

GnomAD4 exome AF: 0.167 AC: 1 AN: 6 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.167 AC: 1 AN: 6

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.127 AC: 19257 AN: 152106 Hom.: 1398 Cov.: 32 AF XY: 0.124 AC XY: 9239 AN XY: 74358

African (AFR) AF: 0.176 AC: 7308 AN: 41490

American (AMR) AF: 0.139 AC: 2128 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 400 AN: 3468

East Asian (EAS) AF: 0.0417 AC: 216 AN: 5178

South Asian (SAS) AF: 0.0731 AC: 352 AN: 4814

European-Finnish (FIN) AF: 0.0852 AC: 901 AN: 10572

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7510 AN: 67986

Other (OTH) AF: 0.130 AC: 274 AN: 2110

Alfa AF: 0.103 Hom.: 791

Bravo AF: 0.134

Asia WGS AF: 0.0840 AC: 293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.88
DANN	Benign	0.37
PhyloP100		0.052
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: rs6700529; hg19: chr1-92236342;