rs10874996

Positions:

• chr1-91834527-G-A
• chr1-91834527-G-C

Variant summary

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

The NM_003243.5(TGFBR3):​c.61+26944C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 151,982 control chromosomes in the GnomAD database, including 7,015 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 0.29 (7015 hom., cov: 32)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24

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 (AFR) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.61+26944C>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.61+26944C>T		intron_variant		1	NM_003243.5	ENSP00000212355	P3

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43503 AN: 151864 Hom.: 6999 Cov.: 32

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.287 AC: 43552 AN: 151982 Hom.: 7015 Cov.: 32 AF XY: 0.286 AC XY: 21273 AN XY: 74296

Gnomad4 AFR AF: 0.433

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.351

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.266

Alfa AF: 0.260 Hom.: 1288

Bravo AF: 0.292

Asia WGS AF: 0.310 AC: 1081 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.3
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10874996; hg19: chr1-92300084;