rs6604050

Variant names:

• chr1-91687934-C-G
• rs6604050
• NM_003243.5:c.2438-4077G>C

Variant summary

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

The NM_003243.5(TGFBR3):​c.2438-4077G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 152,030 control chromosomes in the GnomAD database, including 10,414 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 0.37 (10414 hom., cov: 32)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.688
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.2438-4077G>C		intron_variant	Intron 16 of 16	ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9	c.2438-4077G>C		intron_variant	Intron 16 of 16	1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55519 AN: 151910 Hom.: 10412 Cov.: 32

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.0927

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.365 AC: 55551 AN: 152030 Hom.: 10414 Cov.: 32 AF XY: 0.358 AC XY: 26609 AN XY: 74352

African (AFR) AF: 0.413 AC: 17102 AN: 41446

American (AMR) AF: 0.311 AC: 4744 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1119 AN: 3468

East Asian (EAS) AF: 0.0927 AC: 480 AN: 5178

South Asian (SAS) AF: 0.270 AC: 1302 AN: 4816

European-Finnish (FIN) AF: 0.333 AC: 3527 AN: 10586

Middle Eastern (MID) AF: 0.339 AC: 99 AN: 292

European-Non Finnish (NFE) AF: 0.384 AC: 26065 AN: 67946

Other (OTH) AF: 0.349 AC: 738 AN: 2114

Alfa AF: 0.378 Hom.: 1337

Bravo AF: 0.370

Asia WGS AF: 0.186 AC: 647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.34
DANN	Benign	0.26
PhyloP100		-0.69
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: rs6604050; hg19: chr1-92153491; COSMIC: COSV53023264;