rs12044500

Variant names:

• chr1-91765768-T-C
• rs12044500
• NM_003243.5:c.247-7018A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003243.5(TGFBR3):​c.247-7018A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,250 control chromosomes in the GnomAD database, including 2,187 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 0.15 (2187 hom., cov: 31)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.747
• Publications: 2 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.247-7018A>G		intron_variant	Intron 3 of 16	ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9	c.247-7018A>G		intron_variant	Intron 3 of 16	1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23117 AN: 152132 Hom.: 2188 Cov.: 31

Gnomad AFR AF: 0.0616

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.0383

Gnomad SAS AF: 0.0969

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.152 AC: 23114 AN: 152250 Hom.: 2187 Cov.: 31 AF XY: 0.152 AC XY: 11309 AN XY: 74440

African (AFR) AF: 0.0615 AC: 2555 AN: 41550

American (AMR) AF: 0.129 AC: 1980 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 606 AN: 3470

East Asian (EAS) AF: 0.0380 AC: 197 AN: 5186

South Asian (SAS) AF: 0.0963 AC: 465 AN: 4828

European-Finnish (FIN) AF: 0.270 AC: 2856 AN: 10590

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13851 AN: 68008

Other (OTH) AF: 0.144 AC: 305 AN: 2114

Alfa AF: 0.181 Hom.: 4710

Bravo AF: 0.140

Asia WGS AF: 0.0700 AC: 243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.0
DANN	Benign	0.60
PhyloP100		-0.75
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: rs12044500; hg19: chr1-92231325; COSMIC: COSV53023591;