rs11165441

Variant names:

• chr1-91758790-G-A
• rs11165441
• NM_003243.5:c.247-40C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-91758790-G-A
• chr1-91758790-G-T

Variant summary

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

The NM_003243.5(TGFBR3):​c.247-40C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 1,612,018 control chromosomes in the GnomAD database, including 20,490 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 0.15 (1797 hom., cov: 32)
  • Exomes 𝑓: 0.15 (18693 hom.)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340
• Publications: 12 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=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5	c.247-40C>T		intron_variant	Intron 3 of 16	ENST00000212355.9	NP_003234.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9	c.247-40C>T		intron_variant	Intron 3 of 16	1	NM_003243.5	ENSP00000212355.4

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22576 AN: 151922 Hom.: 1797 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.0829

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.0649

Gnomad FIN AF: 0.0732

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.148

GnomAD2 exomes AF: 0.139 AC: 34961 AN: 250688 AF XY: 0.136

Gnomad AFR exome AF: 0.142

Gnomad AMR exome AF: 0.137

Gnomad ASJ exome AF: 0.0867

Gnomad EAS exome AF: 0.254

Gnomad FIN exome AF: 0.0801

Gnomad NFE exome AF: 0.157

Gnomad OTH exome AF: 0.137

GnomAD4 exome AF: 0.154 AC: 225421 AN: 1459978 Hom.: 18693 Cov.: 33 AF XY: 0.152 AC XY: 110169 AN XY: 726346

African (AFR) AF: 0.141 AC: 4724 AN: 33436

American (AMR) AF: 0.143 AC: 6390 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.0838 AC: 2189 AN: 26112

East Asian (EAS) AF: 0.270 AC: 10717 AN: 39656

South Asian (SAS) AF: 0.0690 AC: 5939 AN: 86104

European-Finnish (FIN) AF: 0.0863 AC: 4602 AN: 53330

Middle Eastern (MID) AF: 0.109 AC: 613 AN: 5630

European-Non Finnish (NFE) AF: 0.163 AC: 181118 AN: 1110726

Other (OTH) AF: 0.151 AC: 9129 AN: 60310

GnomAD4 genome AF: 0.149 AC: 22592 AN: 152040 Hom.: 1797 Cov.: 32 AF XY: 0.144 AC XY: 10730 AN XY: 74334

African (AFR) AF: 0.141 AC: 5859 AN: 41466

American (AMR) AF: 0.174 AC: 2653 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0829 AC: 287 AN: 3464

East Asian (EAS) AF: 0.262 AC: 1350 AN: 5150

South Asian (SAS) AF: 0.0659 AC: 318 AN: 4822

European-Finnish (FIN) AF: 0.0732 AC: 774 AN: 10576

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10873 AN: 67968

Other (OTH) AF: 0.151 AC: 319 AN: 2112

Alfa AF: 0.146 Hom.: 572

Bravo AF: 0.156

Asia WGS AF: 0.157 AC: 545 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.1
DANN	Benign	0.71
PhyloP100		-0.34
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: rs11165441; hg19: chr1-92224347; COSMIC: COSV53029524;