rs2306886

Variant names:

• chr1-91734554-G-A
• rs2306886
• NM_003243.5:c.568+222C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-91734554-G-A
• chr1-91734554-G-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.568+222C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 151,922 control chromosomes in the GnomAD database, including 14,401 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 0.43 (14401 hom., cov: 32)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.466
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.568+222C>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.568+222C>T		intron_variant	Intron 5 of 16	1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65553 AN: 151800 Hom.: 14388 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.432 AC: 65593 AN: 151922 Hom.: 14401 Cov.: 32 AF XY: 0.433 AC XY: 32152 AN XY: 74268

African (AFR) AF: 0.361 AC: 14956 AN: 41412

American (AMR) AF: 0.428 AC: 6529 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 1884 AN: 3468

East Asian (EAS) AF: 0.502 AC: 2584 AN: 5152

South Asian (SAS) AF: 0.486 AC: 2338 AN: 4810

European-Finnish (FIN) AF: 0.465 AC: 4914 AN: 10560

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.455 AC: 30900 AN: 67942

Other (OTH) AF: 0.434 AC: 916 AN: 2110

Alfa AF: 0.448 Hom.: 5319

Bravo AF: 0.423

Asia WGS AF: 0.493 AC: 1713 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.7
DANN	Benign	0.30
PhyloP100		0.47
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: rs2306886; hg19: chr1-92200111; COSMIC: COSV53023471;