rs2229500

Variant names:

• chr1-91719965-G-A
• rs2229500
• NM_003243.5:c.1341C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-91719965-G-A
• chr1-91719965-G-C
• chr1-91719965-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BS1 BS2

The NM_003243.5(TGFBR3):​c.1341C>T​(p.Ser447Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0183 in 1,614,078 control chromosomes in the GnomAD database, including 310 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.016 (30 hom., cov: 32)
  • Exomes 𝑓: 0.019 (280 hom.)
• Consequence: TGFBR3 NM_003243.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.205
• Publications: 3 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 1-91719965-G-A is Benign according to our data. Variant chr1-91719965-G-A is described in ClinVar as Benign. ClinVar VariationId is 3055456.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.205 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0157 (2390/152206) while in subpopulation NFE AF = 0.0207 (1409/68020). AF 95% confidence interval is 0.0198. There are 30 homozygotes in GnomAd4. There are 1243 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2390 AD gene.

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.1341C>T	p.Ser447Ser	synonymous	Exon 9 of 17	NP_003234.2	Q03167-1
	TGFBR3	NM_001195683.2		c.1338C>T	p.Ser446Ser	synonymous	Exon 9 of 17	NP_001182612.1	A0A0A8KWK3
	TGFBR3	NM_001195684.1		c.1338C>T	p.Ser446Ser	synonymous	Exon 10 of 18	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.1341C>T	p.Ser447Ser	synonymous	Exon 9 of 17	ENSP00000212355.4	Q03167-1
	TGFBR3	ENST00000525962.5	TSL:1	c.1341C>T	p.Ser447Ser	synonymous	Exon 8 of 16	ENSP00000436127.1	Q03167-1
	TGFBR3	ENST00000370399.6	TSL:1	c.1338C>T	p.Ser446Ser	synonymous	Exon 10 of 18	ENSP00000359426.2	Q03167-2

Frequencies

GnomAD3 genomes AF: 0.0157 AC: 2389 AN: 152088 Hom.: 30 Cov.: 32

Gnomad AFR AF: 0.00427

Gnomad AMI AF: 0.0165

Gnomad AMR AF: 0.0202

Gnomad ASJ AF: 0.00663

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00416

Gnomad FIN AF: 0.0376

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0207

Gnomad OTH AF: 0.0158

GnomAD2 exomes AF: 0.0154 AC: 3871 AN: 251254 AF XY: 0.0155

Gnomad AFR exome AF: 0.00394

Gnomad AMR exome AF: 0.0107

Gnomad ASJ exome AF: 0.00764

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0397

Gnomad NFE exome AF: 0.0197

Gnomad OTH exome AF: 0.0214

GnomAD4 exome AF: 0.0186 AC: 27169 AN: 1461872 Hom.: 280 Cov.: 32 AF XY: 0.0182 AC XY: 13241 AN XY: 727234

African (AFR) AF: 0.00266 AC: 89 AN: 33480

American (AMR) AF: 0.0117 AC: 522 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00754 AC: 197 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00492 AC: 424 AN: 86256

European-Finnish (FIN) AF: 0.0403 AC: 2153 AN: 53418

Middle Eastern (MID) AF: 0.0163 AC: 94 AN: 5766

European-Non Finnish (NFE) AF: 0.0205 AC: 22742 AN: 1111996

Other (OTH) AF: 0.0157 AC: 948 AN: 60396

GnomAD4 genome AF: 0.0157 AC: 2390 AN: 152206 Hom.: 30 Cov.: 32 AF XY: 0.0167 AC XY: 1243 AN XY: 74408

African (AFR) AF: 0.00429 AC: 178 AN: 41532

American (AMR) AF: 0.0201 AC: 308 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00663 AC: 23 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.00437 AC: 21 AN: 4808

European-Finnish (FIN) AF: 0.0376 AC: 399 AN: 10600

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0207 AC: 1409 AN: 68020

Other (OTH) AF: 0.0156 AC: 33 AN: 2112

Alfa AF: 0.0131 Hom.: 15

Bravo AF: 0.0137

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.0210

EpiControl AF: 0.0209

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	TGFBR3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.7
DANN	Benign	0.56
PhyloP100		0.20
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2229500; hg19: chr1-92185522;