1-91780491-C-G

Variant names:

• chr1-91780491-C-G
• rs17443164
• NM_003243.5:c.246+16796G>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.246+16796G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 148,588 control chromosomes in the GnomAD database, including 7,199 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 0.31 (7199 hom., cov: 28)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.550
• Publications: 4 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=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.354 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBR3	NM_003243.5	MANE Select	c.246+16796G>C		intron	N/A	NP_003234.2
	TGFBR3	NM_001195683.2		c.246+16796G>C		intron	N/A	NP_001182612.1
	TGFBR3	NM_001195684.1		c.246+16796G>C		intron	N/A	NP_001182613.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBR3	ENST00000212355.9	TSL:1 MANE Select	c.246+16796G>C		intron	N/A	ENSP00000212355.4
	TGFBR3	ENST00000525962.5	TSL:1	c.246+16796G>C		intron	N/A	ENSP00000436127.1
	TGFBR3	ENST00000370399.6	TSL:1	c.246+16796G>C		intron	N/A	ENSP00000359426.2

Frequencies

GnomAD3 genomes AF: 0.306 AC: 45414 AN: 148508 Hom.: 7191 Cov.: 28

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.0531

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.448

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.306 AC: 45451 AN: 148588 Hom.: 7199 Cov.: 28 AF XY: 0.304 AC XY: 22005 AN XY: 72266

African (AFR) AF: 0.311 AC: 12485 AN: 40178

American (AMR) AF: 0.335 AC: 4995 AN: 14898

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1280 AN: 3444

East Asian (EAS) AF: 0.0533 AC: 265 AN: 4972

South Asian (SAS) AF: 0.368 AC: 1735 AN: 4714

European-Finnish (FIN) AF: 0.257 AC: 2484 AN: 9672

Middle Eastern (MID) AF: 0.472 AC: 136 AN: 288

European-Non Finnish (NFE) AF: 0.314 AC: 21178 AN: 67466

Other (OTH) AF: 0.327 AC: 671 AN: 2052

Alfa AF: 0.307 Hom.: 898

Bravo AF: 0.307

Asia WGS AF: 0.215 AC: 748 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.46
DANN	Benign	0.30
PhyloP100		-0.55
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: rs17443164; hg19: chr1-92246048; COSMIC: COSV53030779;