chr1-91749071-T-C

Position:

• chr1-91749071-T-C

Variant summary

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

The ENST00000212355.9(TGFBR3):​c.384+9542A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 152,120 control chromosomes in the GnomAD database, including 57,009 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 0.86 (57009 hom., cov: 31)
• Consequence: TGFBR3 ENST00000212355.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0910

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 (AFR) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.384+9542A>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.384+9542A>G		intron_variant		1	NM_003243.5	ENSP00000212355	P3

Frequencies

GnomAD3 genomes AF: 0.864 AC: 131357 AN: 152002 Hom.: 56949 Cov.: 31

Gnomad AFR AF: 0.929

Gnomad AMI AF: 0.795

Gnomad AMR AF: 0.854

Gnomad ASJ AF: 0.797

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.755

Gnomad FIN AF: 0.857

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.850

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

GnomAD4 genome AF: 0.864 AC: 131476 AN: 152120 Hom.: 57009 Cov.: 31 AF XY: 0.863 AC XY: 64146 AN XY: 74342

Gnomad4 AFR AF: 0.930

Gnomad4 AMR AF: 0.854

Gnomad4 ASJ AF: 0.797

Gnomad4 EAS AF: 0.799

Gnomad4 SAS AF: 0.756

Gnomad4 FIN AF: 0.857

Gnomad4 NFE AF: 0.845

Gnomad4 OTH AF: 0.850

Alfa AF: 0.845 Hom.: 68951

Bravo AF: 0.867

Asia WGS AF: 0.766 AC: 2666 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	4.2
DANN	Benign	0.58

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: rs284170; hg19: chr1-92214628;