NM_003243.5:c.-113-8883A>C

Variant names:

• chr1-91870527-T-G
• rs6656018
• NM_003243.5:c.-113-8883A>C

Variant summary

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

The NM_003243.5(TGFBR3):​c.-113-8883A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 152,106 control chromosomes in the GnomAD database, including 30,513 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 0.63 (30513 hom., cov: 33)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.100
• Publications: 5 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003243.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBR3	NM_003243.5	MANE Select	c.-113-8883A>C		intron	N/A	NP_003234.2	Q03167-1
	TGFBR3	NM_001195683.2		c.-113-8883A>C		intron	N/A	NP_001182612.1	A0A0A8KWK3
	TGFBR3	NM_001195684.1		c.-113-8883A>C		intron	N/A	NP_001182613.1	A0A0A8KWK3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBR3	ENST00000212355.9	TSL:1 MANE Select	c.-113-8883A>C		intron	N/A	ENSP00000212355.4	Q03167-1
	TGFBR3	ENST00000370399.6	TSL:1	c.-113-8883A>C		intron	N/A	ENSP00000359426.2	Q03167-2
	TGFBR3	ENST00000465892.6	TSL:1	c.-113-8883A>C		intron	N/A	ENSP00000432638.1	Q03167-2

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95853 AN: 151988 Hom.: 30500 Cov.: 33

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.639

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

GnomAD4 genome AF: 0.631 AC: 95907 AN: 152106 Hom.: 30513 Cov.: 33 AF XY: 0.624 AC XY: 46410 AN XY: 74342

African (AFR) AF: 0.598 AC: 24804 AN: 41486

American (AMR) AF: 0.628 AC: 9588 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2234 AN: 3464

East Asian (EAS) AF: 0.386 AC: 1995 AN: 5174

South Asian (SAS) AF: 0.596 AC: 2870 AN: 4816

European-Finnish (FIN) AF: 0.574 AC: 6076 AN: 10592

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.680 AC: 46211 AN: 67988

Other (OTH) AF: 0.633 AC: 1336 AN: 2110

Alfa AF: 0.638 Hom.: 5202

Bravo AF: 0.633

Asia WGS AF: 0.473 AC: 1647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.6
DANN	Benign	0.62
PhyloP100		-0.10
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: rs6656018; hg19: chr1-92336084;