rs1805113

Variant names:

• chr1-91712381-A-G
• rs1805113
• NM_003243.5:c.2028T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-91712381-A-G
• chr1-91712381-A-C
• chr1-91712381-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_003243.5(TGFBR3):​c.2028T>C​(p.Phe676Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 1,613,752 control chromosomes in the GnomAD database, including 138,697 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.38 (11178 hom., cov: 33)
  • Exomes 𝑓: 0.41 (127519 hom.)
• Consequence: TGFBR3 NM_003243.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.519
• Publications: 38 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=-0.61).
• BP6: Variant 1-91712381-A-G is Benign according to our data. Variant chr1-91712381-A-G is described in ClinVar as Benign. ClinVar VariationId is 3059465.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.519 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.436 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.2028T>C	p.Phe676Phe	synonymous	Exon 13 of 17	NP_003234.2	Q03167-1
	TGFBR3	NM_001195683.2		c.2025T>C	p.Phe675Phe	synonymous	Exon 13 of 17	NP_001182612.1	A0A0A8KWK3
	TGFBR3	NM_001195684.1		c.2025T>C	p.Phe675Phe	synonymous	Exon 14 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.2028T>C	p.Phe676Phe	synonymous	Exon 13 of 17	ENSP00000212355.4	Q03167-1
	TGFBR3	ENST00000525962.5	TSL:1	c.2028T>C	p.Phe676Phe	synonymous	Exon 12 of 16	ENSP00000436127.1	Q03167-1
	TGFBR3	ENST00000370399.6	TSL:1	c.2025T>C	p.Phe675Phe	synonymous	Exon 14 of 18	ENSP00000359426.2	Q03167-2

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57096 AN: 151972 Hom.: 11165 Cov.: 33

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.0885

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.361

GnomAD2 exomes AF: 0.359 AC: 90265 AN: 251288 AF XY: 0.362

Gnomad AFR exome AF: 0.336

Gnomad AMR exome AF: 0.288

Gnomad ASJ exome AF: 0.341

Gnomad EAS exome AF: 0.104

Gnomad FIN exome AF: 0.359

Gnomad NFE exome AF: 0.445

Gnomad OTH exome AF: 0.385

GnomAD4 exome AF: 0.410 AC: 599306 AN: 1461660 Hom.: 127519 Cov.: 52 AF XY: 0.407 AC XY: 296011 AN XY: 727150

African (AFR) AF: 0.337 AC: 11271 AN: 33480

American (AMR) AF: 0.291 AC: 13022 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 8975 AN: 26136

East Asian (EAS) AF: 0.0903 AC: 3586 AN: 39694

South Asian (SAS) AF: 0.290 AC: 25048 AN: 86254

European-Finnish (FIN) AF: 0.370 AC: 19738 AN: 53416

Middle Eastern (MID) AF: 0.377 AC: 2175 AN: 5768

European-Non Finnish (NFE) AF: 0.443 AC: 492341 AN: 1111802

Other (OTH) AF: 0.383 AC: 23150 AN: 60388

GnomAD4 genome AF: 0.376 AC: 57139 AN: 152092 Hom.: 11178 Cov.: 33 AF XY: 0.366 AC XY: 27229 AN XY: 74350

African (AFR) AF: 0.343 AC: 14218 AN: 41472

American (AMR) AF: 0.327 AC: 5004 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1203 AN: 3464

East Asian (EAS) AF: 0.0887 AC: 460 AN: 5186

South Asian (SAS) AF: 0.276 AC: 1331 AN: 4818

European-Finnish (FIN) AF: 0.349 AC: 3693 AN: 10568

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.440 AC: 29918 AN: 67976

Other (OTH) AF: 0.359 AC: 760 AN: 2116

Alfa AF: 0.416 Hom.: 47586

Bravo AF: 0.375

Asia WGS AF: 0.210 AC: 729 AN: 3478

EpiCase AF: 0.440

EpiControl AF: 0.442

ClinVar

ClinVar submissions

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	-0.61
CADD	Benign	6.7
DANN	Benign	0.54
PhyloP100		0.52
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)		0.0		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: rs1805113; hg19: chr1-92177938; COSMIC: COSV53021858; COSMIC: COSV53021858;