rs17881268

Variant names:

• chr1-91797522-G-A
• rs17881268
• NM_003243.5:c.62-51C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-91797522-G-A
• chr1-91797522-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_003243.5(TGFBR3):​c.62-51C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0262 in 1,607,956 control chromosomes in the GnomAD database, including 688 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 0.018 (36 hom., cov: 33)
  • Exomes 𝑓: 0.027 (652 hom.)
• Consequence: TGFBR3 NM_003243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260
• Publications: 5 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=-0.82).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0176 (2675/152342) while in subpopulation NFE AF = 0.0298 (2025/68038). AF 95% confidence interval is 0.0287. There are 36 homozygotes in GnomAd4. There are 1222 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2675 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.62-51C>T		intron	N/A	NP_003234.2	Q03167-1
	TGFBR3	NM_001195683.2		c.62-51C>T		intron	N/A	NP_001182612.1	A0A0A8KWK3
	TGFBR3	NM_001195684.1		c.62-51C>T		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.62-51C>T		intron	N/A	ENSP00000212355.4	Q03167-1
	TGFBR3	ENST00000525962.5	TSL:1	c.62-51C>T		intron	N/A	ENSP00000436127.1	Q03167-1
	TGFBR3	ENST00000370399.6	TSL:1	c.62-51C>T		intron	N/A	ENSP00000359426.2	Q03167-2

Frequencies

GnomAD3 genomes AF: 0.0176 AC: 2677 AN: 152224 Hom.: 36 Cov.: 33

Gnomad AFR AF: 0.00526

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00700

Gnomad ASJ AF: 0.00518

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0197

Gnomad FIN AF: 0.0173

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0298

Gnomad OTH AF: 0.0120

GnomAD2 exomes AF: 0.0183 AC: 4523 AN: 246576 AF XY: 0.0192

Gnomad AFR exome AF: 0.00487

Gnomad AMR exome AF: 0.00677

Gnomad ASJ exome AF: 0.00714

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0179

Gnomad NFE exome AF: 0.0279

Gnomad OTH exome AF: 0.0187

GnomAD4 exome AF: 0.0271 AC: 39406 AN: 1455614 Hom.: 652 Cov.: 31 AF XY: 0.0267 AC XY: 19323 AN XY: 724560

African (AFR) AF: 0.00513 AC: 171 AN: 33336

American (AMR) AF: 0.00687 AC: 307 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.00797 AC: 208 AN: 26082

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39670

South Asian (SAS) AF: 0.0188 AC: 1616 AN: 85876

European-Finnish (FIN) AF: 0.0174 AC: 928 AN: 53378

Middle Eastern (MID) AF: 0.00608 AC: 35 AN: 5754

European-Non Finnish (NFE) AF: 0.0314 AC: 34805 AN: 1106706

Other (OTH) AF: 0.0221 AC: 1331 AN: 60154

GnomAD4 genome AF: 0.0176 AC: 2675 AN: 152342 Hom.: 36 Cov.: 33 AF XY: 0.0164 AC XY: 1222 AN XY: 74494

African (AFR) AF: 0.00527 AC: 219 AN: 41586

American (AMR) AF: 0.00699 AC: 107 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00518 AC: 18 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.0191 AC: 92 AN: 4824

European-Finnish (FIN) AF: 0.0173 AC: 184 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0298 AC: 2025 AN: 68038

Other (OTH) AF: 0.0118 AC: 25 AN: 2112

Alfa AF: 0.0243 Hom.: 19

Bravo AF: 0.0160

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.91
DANN	Benign	0.44
PhyloP100		0.026
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs17881268;

hg19: chr1-92263079;