chr1-91739530-T-C

Position:

• chr1-91739530-T-C

Variant summary

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

The NM_003243.5(TGFBR3):​c.385-4571A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,182 control chromosomes in the GnomAD database, including 1,229 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 0.12 (1229 hom., cov: 32)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.222

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.385-4571A>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.385-4571A>G		intron_variant		1	NM_003243.5	ENSP00000212355	P3

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18083 AN: 152064 Hom.: 1232 Cov.: 32

Gnomad AFR AF: 0.0809

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.119 AC: 18081 AN: 152182 Hom.: 1229 Cov.: 32 AF XY: 0.126 AC XY: 9339 AN XY: 74398

Gnomad4 AFR AF: 0.0807

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.251

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.116

Alfa AF: 0.120 Hom.: 210

Bravo AF: 0.110

Asia WGS AF: 0.253 AC: 875 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.7
DANN	Benign	0.51

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: rs17131544; hg19: chr1-92205087;