chr1-91758790-G-A

Position:

• chr1-91758790-G-A

Variant summary

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

The NM_003243.5(TGFBR3):​c.247-40C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 1,612,018 control chromosomes in the GnomAD database, including 20,490 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 0.15 (1797 hom., cov: 32)
  • Exomes 𝑓: 0.15 (18693 hom.)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.247-40C>T		intron_variant		ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9	c.247-40C>T		intron_variant		1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22576 AN: 151922 Hom.: 1797 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.0829

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.0649

Gnomad FIN AF: 0.0732

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.148

GnomAD3 exomes AF: 0.139 AC: 34961 AN: 250688 Hom.: 2803 AF XY: 0.136 AC XY: 18386 AN XY: 135458

Gnomad AFR exome AF: 0.142

Gnomad AMR exome AF: 0.137

Gnomad ASJ exome AF: 0.0867

Gnomad EAS exome AF: 0.254

Gnomad SAS exome AF: 0.0661

Gnomad FIN exome AF: 0.0801

Gnomad NFE exome AF: 0.157

Gnomad OTH exome AF: 0.137

GnomAD4 exome AF: 0.154 AC: 225421 AN: 1459978 Hom.: 18693 Cov.: 33 AF XY: 0.152 AC XY: 110169 AN XY: 726346

Gnomad4 AFR exome AF: 0.141

Gnomad4 AMR exome AF: 0.143

Gnomad4 ASJ exome AF: 0.0838

Gnomad4 EAS exome AF: 0.270

Gnomad4 SAS exome AF: 0.0690

Gnomad4 FIN exome AF: 0.0863

Gnomad4 NFE exome AF: 0.163

Gnomad4 OTH exome AF: 0.151

GnomAD4 genome AF: 0.149 AC: 22592 AN: 152040 Hom.: 1797 Cov.: 32 AF XY: 0.144 AC XY: 10730 AN XY: 74334

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.0829

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.0659

Gnomad4 FIN AF: 0.0732

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.151

Alfa AF: 0.144 Hom.: 370

Bravo AF: 0.156

Asia WGS AF: 0.157 AC: 545 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.1
DANN	Benign	0.71

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: rs11165441; hg19: chr1-92224347; COSMIC: COSV53029524;