1-91870349-T-C

Variant names:

• chr1-91870349-T-C
• rs9661103
• NM_003243.5:c.-113-8705A>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.-113-8705A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 152,082 control chromosomes in the GnomAD database, including 33,373 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 0.66 (33373 hom., cov: 33)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454
• Publications: 8 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.679 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.-113-8705A>G		intron	N/A	NP_003234.2	Q03167-1
	TGFBR3	NM_001195683.2		c.-113-8705A>G		intron	N/A	NP_001182612.1	A0A0A8KWK3
	TGFBR3	NM_001195684.1		c.-113-8705A>G		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.-113-8705A>G		intron	N/A	ENSP00000212355.4	Q03167-1
	TGFBR3	ENST00000370399.6	TSL:1	c.-113-8705A>G		intron	N/A	ENSP00000359426.2	Q03167-2
	TGFBR3	ENST00000465892.6	TSL:1	c.-113-8705A>G		intron	N/A	ENSP00000432638.1	Q03167-2

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100283 AN: 151964 Hom.: 33351 Cov.: 33

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.665

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.672

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

GnomAD4 genome AF: 0.660 AC: 100352 AN: 152082 Hom.: 33373 Cov.: 33 AF XY: 0.654 AC XY: 48588 AN XY: 74342

African (AFR) AF: 0.685 AC: 28434 AN: 41480

American (AMR) AF: 0.647 AC: 9881 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 2307 AN: 3468

East Asian (EAS) AF: 0.407 AC: 2102 AN: 5160

South Asian (SAS) AF: 0.598 AC: 2878 AN: 4816

European-Finnish (FIN) AF: 0.574 AC: 6068 AN: 10566

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.684 AC: 46478 AN: 67998

Other (OTH) AF: 0.666 AC: 1407 AN: 2114

Alfa AF: 0.674 Hom.: 19442

Bravo AF: 0.666

Asia WGS AF: 0.503 AC: 1753 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.2
DANN	Benign	0.83
PhyloP100		-0.45
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: rs9661103; hg19: chr1-92335906;