1-91866932-C-T

Variant names:

• chr1-91866932-C-T
• rs2489188
• NM_003243.5:c.-113-5288G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.91).
• 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 rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.-113-5288G>A		intron_variant	Intron 1 of 16	ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9	c.-113-5288G>A		intron_variant	Intron 1 of 16	1	NM_003243.5	ENSP00000212355.4

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

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) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.833 AC: 15 AN: 18

Other (OTH) AF: 1.00 AC: 4 AN: 4

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

African (AFR) AF: 0.621 AC: 25746 AN: 41472

American (AMR) AF: 0.661 AC: 10093 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2243 AN: 3470

East Asian (EAS) AF: 0.806 AC: 4171 AN: 5172

South Asian (SAS) AF: 0.694 AC: 3348 AN: 4822

European-Finnish (FIN) AF: 0.614 AC: 6491 AN: 10566

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.666 AC: 45236 AN: 67970

Other (OTH) AF: 0.656 AC: 1386 AN: 2114

Alfa AF: 0.664 Hom.: 18430

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
PhyloP100		-1.5
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: rs2489188; hg19: chr1-92332489;