chr1-91792093-G-C

Position:

• chr1-91792093-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003243.5(TGFBR3):​c.246+5194C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,196 control chromosomes in the GnomAD database, including 3,192 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 0.17 (3192 hom., cov: 33)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

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]

TGFBR3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.246+5194C>G		intron_variant		ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9	c.246+5194C>G		intron_variant		1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25787 AN: 152078 Hom.: 3178 Cov.: 33

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.0847

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.0866

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.170 AC: 25831 AN: 152196 Hom.: 3192 Cov.: 33 AF XY: 0.172 AC XY: 12809 AN XY: 74420

Gnomad4 AFR AF: 0.339

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.0847

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.0866

Gnomad4 OTH AF: 0.149

Alfa AF: 0.0578 Hom.: 61

Bravo AF: 0.177

Asia WGS AF: 0.230 AC: 804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	15
DANN	Benign	0.81

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: rs6678564; hg19: chr1-92257650;