rs2489188

Positions:

• chr1-91866932-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003243.5(TGFBR3):​c.-113-5288G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 152,076 control chromosomes in the GnomAD database, including 32,620 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 0.65 (32612 hom., cov: 32)
  • Exomes 𝑓: 0.79 (8 hom.)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.-113-5288G>A		intron_variant		ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9	c.-113-5288G>A		intron_variant		1	NM_003243.5	ENSP00000212355	P3

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99429 AN: 151934 Hom.: 32593 Cov.: 32

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.653

GnomAD4 exome AF: 0.792 AC: 19 AN: 24 Hom.: 8 AF XY: 0.864 AC XY: 19 AN XY: 22

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.833

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.654 AC: 99487 AN: 152052 Hom.: 32612 Cov.: 32 AF XY: 0.652 AC XY: 48467 AN XY: 74326

Gnomad4 AFR AF: 0.621

Gnomad4 AMR AF: 0.661

Gnomad4 ASJ AF: 0.646

Gnomad4 EAS AF: 0.806

Gnomad4 SAS AF: 0.694

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.666

Gnomad4 OTH AF: 0.656

Alfa AF: 0.664 Hom.: 16540

Bravo AF: 0.657

Asia WGS AF: 0.691 AC: 2403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.29
DANN	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs2489188; hg19: chr1-92332489;