1-91707051-A-G

Variant names:

• chr1-91707051-A-G
• rs6660484
• NM_003243.5:c.2287+1612T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003243.5(TGFBR3):​c.2287+1612T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 152,102 control chromosomes in the GnomAD database, including 11,612 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 0.39 (11612 hom., cov: 33)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.191
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003243.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBR3	NM_003243.5	MANE Select	c.2287+1612T>C		intron	N/A	NP_003234.2
	TGFBR3	NM_001195683.2		c.2284+1612T>C		intron	N/A	NP_001182612.1
	TGFBR3	NM_001195684.1		c.2284+1612T>C		intron	N/A	NP_001182613.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBR3	ENST00000212355.9	TSL:1 MANE Select	c.2287+1612T>C		intron	N/A	ENSP00000212355.4
	TGFBR3	ENST00000525962.5	TSL:1	c.2287+1612T>C		intron	N/A	ENSP00000436127.1
	TGFBR3	ENST00000370399.6	TSL:1	c.2284+1612T>C		intron	N/A	ENSP00000359426.2

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58856 AN: 151984 Hom.: 11576 Cov.: 33

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.387 AC: 58932 AN: 152102 Hom.: 11612 Cov.: 33 AF XY: 0.389 AC XY: 28908 AN XY: 74356

African (AFR) AF: 0.373 AC: 15500 AN: 41508

American (AMR) AF: 0.346 AC: 5290 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 845 AN: 3470

East Asian (EAS) AF: 0.469 AC: 2428 AN: 5178

South Asian (SAS) AF: 0.241 AC: 1164 AN: 4826

European-Finnish (FIN) AF: 0.491 AC: 5189 AN: 10558

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.401 AC: 27242 AN: 67966

Other (OTH) AF: 0.373 AC: 786 AN: 2108

Alfa AF: 0.395 Hom.: 53888

Bravo AF: 0.379

Asia WGS AF: 0.377 AC: 1311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.6
DANN	Benign	0.68
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6660484; hg19: chr1-92172608;