1-91724546-G-C

Variant names:

• chr1-91724546-G-C
• rs12562433
• NM_003243.5:c.886-2402C>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003243.5(TGFBR3):​c.886-2402C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 152,060 control chromosomes in the GnomAD database, including 12,238 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 0.39 (12238 hom., cov: 32)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.786
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.886-2402C>G		intron_variant	Intron 7 of 16	ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9	c.886-2402C>G		intron_variant	Intron 7 of 16	1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59936 AN: 151942 Hom.: 12235 Cov.: 32

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.394 AC: 59971 AN: 152060 Hom.: 12238 Cov.: 32 AF XY: 0.398 AC XY: 29584 AN XY: 74334

African (AFR) AF: 0.319 AC: 13209 AN: 41460

American (AMR) AF: 0.345 AC: 5279 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 1489 AN: 3468

East Asian (EAS) AF: 0.494 AC: 2556 AN: 5170

South Asian (SAS) AF: 0.450 AC: 2170 AN: 4822

European-Finnish (FIN) AF: 0.484 AC: 5110 AN: 10556

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.422 AC: 28714 AN: 67988

Other (OTH) AF: 0.397 AC: 837 AN: 2108

Alfa AF: 0.395 Hom.: 1539

Bravo AF: 0.378

Asia WGS AF: 0.471 AC: 1636 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	14
DANN	Benign	0.67
PhyloP100		0.79
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: rs12562433; hg19: chr1-92190103;