rs11578802

Variant names:

• chr1-91732120-G-A
• rs11578802
• NM_003243.5:c.569-2147C>T

Variant summary

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

The NM_003243.5(TGFBR3):​c.569-2147C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 151,894 control chromosomes in the GnomAD database, including 30,548 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 0.62 (30548 hom., cov: 31)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.569-2147C>T		intron_variant	Intron 5 of 16	ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9	c.569-2147C>T		intron_variant	Intron 5 of 16	1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94776 AN: 151774 Hom.: 30533 Cov.: 31

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.639

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.836

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.660

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

GnomAD4 genome AF: 0.624 AC: 94830 AN: 151894 Hom.: 30548 Cov.: 31 AF XY: 0.625 AC XY: 46362 AN XY: 74232

African (AFR) AF: 0.456 AC: 18868 AN: 41406

American (AMR) AF: 0.687 AC: 10502 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.836 AC: 2900 AN: 3470

East Asian (EAS) AF: 0.542 AC: 2790 AN: 5152

South Asian (SAS) AF: 0.817 AC: 3927 AN: 4804

European-Finnish (FIN) AF: 0.621 AC: 6544 AN: 10544

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.694 AC: 47110 AN: 67924

Other (OTH) AF: 0.658 AC: 1385 AN: 2106

Alfa AF: 0.669 Hom.: 23200

Bravo AF: 0.617

Asia WGS AF: 0.665 AC: 2313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.3
DANN	Benign	0.53
PhyloP100		1.1
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: rs11578802; hg19: chr1-92197677;