1-91737326-C-G

Position:

• chr1-91737326-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003243.5(TGFBR3):​c.385-2367G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,150 control chromosomes in the GnomAD database, including 2,155 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 0.16 (2155 hom., cov: 32)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFBR3	NM_003243.5	c.385-2367G>C		intron_variant		ENST00000212355.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFBR3	ENST00000212355.9	c.385-2367G>C		intron_variant		1	NM_003243.5	P3

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24383 AN: 152032 Hom.: 2157 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.160 AC: 24394 AN: 152150 Hom.: 2155 Cov.: 32 AF XY: 0.167 AC XY: 12391 AN XY: 74380

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.146

Alfa AF: 0.145 Hom.: 223

Bravo AF: 0.158

Asia WGS AF: 0.273 AC: 945 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.6
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs923378; hg19: chr1-92202883;