rs4658261

Variant names:

• chr1-91719187-C-T
• rs4658261
• NM_003243.5:c.1566+125G>A

Variant summary

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

The NM_003243.5(TGFBR3):​c.1566+125G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 1,293,332 control chromosomes in the GnomAD database, including 36,376 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.21 (3684 hom., cov: 32)
  • Exomes 𝑓: 0.23 (32692 hom.)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 7 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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.289 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBR3	NM_003243.5	MANE Select	c.1566+125G>A		intron	N/A	NP_003234.2	Q03167-1
	TGFBR3	NM_001195683.2		c.1563+125G>A		intron	N/A	NP_001182612.1	A0A0A8KWK3
	TGFBR3	NM_001195684.1		c.1563+125G>A		intron	N/A	NP_001182613.1	A0A0A8KWK3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBR3	ENST00000212355.9	TSL:1 MANE Select	c.1566+125G>A		intron	N/A	ENSP00000212355.4	Q03167-1
	TGFBR3	ENST00000525962.5	TSL:1	c.1566+125G>A		intron	N/A	ENSP00000436127.1	Q03167-1
	TGFBR3	ENST00000370399.6	TSL:1	c.1563+125G>A		intron	N/A	ENSP00000359426.2	Q03167-2

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31913 AN: 152058 Hom.: 3676 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.0399

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.231

GnomAD4 exome AF: 0.232 AC: 264539 AN: 1141156 Hom.: 32692 AF XY: 0.235 AC XY: 135657 AN XY: 577036

African (AFR) AF: 0.162 AC: 4373 AN: 26984

American (AMR) AF: 0.311 AC: 11396 AN: 36634

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 6805 AN: 22922

East Asian (EAS) AF: 0.0792 AC: 2895 AN: 36566

South Asian (SAS) AF: 0.315 AC: 23395 AN: 74192

European-Finnish (FIN) AF: 0.133 AC: 6720 AN: 50466

Middle Eastern (MID) AF: 0.328 AC: 1671 AN: 5102

European-Non Finnish (NFE) AF: 0.233 AC: 195797 AN: 838702

Other (OTH) AF: 0.232 AC: 11487 AN: 49588

GnomAD4 genome AF: 0.210 AC: 31944 AN: 152176 Hom.: 3684 Cov.: 32 AF XY: 0.207 AC XY: 15434 AN XY: 74396

African (AFR) AF: 0.170 AC: 7051 AN: 41516

American (AMR) AF: 0.271 AC: 4150 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1009 AN: 3472

East Asian (EAS) AF: 0.0402 AC: 208 AN: 5174

South Asian (SAS) AF: 0.302 AC: 1454 AN: 4814

European-Finnish (FIN) AF: 0.138 AC: 1464 AN: 10600

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15892 AN: 67996

Other (OTH) AF: 0.232 AC: 491 AN: 2114

Alfa AF: 0.222 Hom.: 825

Bravo AF: 0.216

Asia WGS AF: 0.164 AC: 574 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.3
DANN	Benign	0.69
PhyloP100		0.0
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: rs4658261; hg19: chr1-92184744;