1-91822380-C-G

Variant names:

• chr1-91822380-C-G
• rs10493858
• NM_003243.5:c.62-24909G>C

Variant summary

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

The NM_003243.5(TGFBR3):​c.62-24909G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 147,186 control chromosomes in the GnomAD database, including 6,372 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 0.28 (6372 hom., cov: 26)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.896

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.62-24909G>C		intron_variant	Intron 2 of 16	ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9	c.62-24909G>C		intron_variant	Intron 2 of 16	1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.282 AC: 41444 AN: 147100 Hom.: 6362 Cov.: 26

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.282 AC: 41472 AN: 147186 Hom.: 6372 Cov.: 26 AF XY: 0.282 AC XY: 20137 AN XY: 71532

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.255

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.260

Alfa AF: 0.113 Hom.: 147

Bravo AF: 0.285

Asia WGS AF: 0.305 AC: 1064 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.1
DANN	Benign	0.70

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: rs10493858; hg19: chr1-92287937;