rs1805110

Variant names:

• chr1-91861488-G-A
• rs1805110
• NM_003243.5:c.44C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-91861488-G-A
• chr1-91861488-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_003243.5(TGFBR3):​c.44C>T​(p.Ser15Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,612,018 control chromosomes in the GnomAD database, including 11,638 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.13 (1643 hom., cov: 32)
  • Exomes 𝑓: 0.10 (9995 hom.)
• Consequence: TGFBR3 NM_003243.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.65
• Publications: 42 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004665315).
• BP6: Variant 1-91861488-G-A is Benign according to our data. Variant chr1-91861488-G-A is described in ClinVar as Benign. ClinVar VariationId is 3060183.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.44C>T	p.Ser15Phe	missense_variant	Exon 2 of 17	ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9	c.44C>T	p.Ser15Phe	missense_variant	Exon 2 of 17	1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19741 AN: 151990 Hom.: 1635 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.0936

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0844

Gnomad OTH AF: 0.121

GnomAD2 exomes AF: 0.131 AC: 33006 AN: 251414 AF XY: 0.129

Gnomad AFR exome AF: 0.183

Gnomad AMR exome AF: 0.126

Gnomad ASJ exome AF: 0.132

Gnomad EAS exome AF: 0.397

Gnomad FIN exome AF: 0.113

Gnomad NFE exome AF: 0.0856

Gnomad OTH exome AF: 0.109

GnomAD4 exome AF: 0.100 AC: 146296 AN: 1459910 Hom.: 9995 Cov.: 30 AF XY: 0.101 AC XY: 73264 AN XY: 726348

African (AFR) AF: 0.180 AC: 6009 AN: 33428

American (AMR) AF: 0.128 AC: 5741 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 3524 AN: 26114

East Asian (EAS) AF: 0.417 AC: 16534 AN: 39654

South Asian (SAS) AF: 0.135 AC: 11603 AN: 86214

European-Finnish (FIN) AF: 0.110 AC: 5856 AN: 53392

Middle Eastern (MID) AF: 0.0770 AC: 444 AN: 5766

European-Non Finnish (NFE) AF: 0.0809 AC: 89860 AN: 1110316

Other (OTH) AF: 0.112 AC: 6725 AN: 60312

GnomAD4 genome AF: 0.130 AC: 19782 AN: 152108 Hom.: 1643 Cov.: 32 AF XY: 0.132 AC XY: 9792 AN XY: 74360

African (AFR) AF: 0.180 AC: 7452 AN: 41460

American (AMR) AF: 0.121 AC: 1848 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 464 AN: 3466

East Asian (EAS) AF: 0.397 AC: 2057 AN: 5178

South Asian (SAS) AF: 0.140 AC: 674 AN: 4808

European-Finnish (FIN) AF: 0.110 AC: 1167 AN: 10588

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0844 AC: 5740 AN: 68008

Other (OTH) AF: 0.127 AC: 269 AN: 2116

Alfa AF: 0.105 Hom.: 4864

Bravo AF: 0.135

TwinsUK AF: 0.0833 AC: 309

ALSPAC AF: 0.0838 AC: 323

ESP6500AA AF: 0.175 AC: 771

ESP6500EA AF: 0.0848 AC: 729

ExAC AF: 0.131 AC: 15872

Asia WGS AF: 0.236 AC: 819 AN: 3478

EpiCase AF: 0.0852

EpiControl AF: 0.0836

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

TGFBR3-related disorder Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Benign	0.93
DEOGEN2	Benign	0.11	T;.;T;.;.
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.83	T;.;.;T;T
MetaRNN	Benign	0.0047	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;L;L;L;.
PhyloP100		1.7
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.25	N;N;N;N;D
REVEL	Benign	0.094
Sift	Benign	0.17	T;T;T;T;T
Sift4G	Benign	0.70	T;T;T;T;.
Polyphen		0.0	B;B;B;B;.
Vest4		0.12
MPC		0.25
ClinPred		0.0078	T
GERP RS		3.2
PromoterAI		0.00040	Neutral
Varity_R		0.058
gMVP		0.15
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: rs1805110; hg19: chr1-92327045; COSMIC: COSV53023135; COSMIC: COSV53023135;