rs2279455

Positions:

• chr1-91719628-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.1414-164A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 151,864 control chromosomes in the GnomAD database, including 27,304 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 0.60 (27304 hom., cov: 30)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFBR3	NM_003243.5	c.1414-164A>G		intron_variant		ENST00000212355.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFBR3	ENST00000212355.9	c.1414-164A>G		intron_variant		1	NM_003243.5	P3

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90623 AN: 151746 Hom.: 27265 Cov.: 30

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.609

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

GnomAD4 genome AF: 0.597 AC: 90716 AN: 151864 Hom.: 27304 Cov.: 30 AF XY: 0.597 AC XY: 44287 AN XY: 74190

Gnomad4 AFR AF: 0.625

Gnomad4 AMR AF: 0.584

Gnomad4 ASJ AF: 0.634

Gnomad4 EAS AF: 0.325

Gnomad4 SAS AF: 0.695

Gnomad4 FIN AF: 0.575

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.608

Alfa AF: 0.604 Hom.: 36786

Bravo AF: 0.594

Asia WGS AF: 0.533 AC: 1854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.0
DANN	Benign	0.62

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: rs2279455; hg19: chr1-92185185;