chr9-99146083-T-G

Variant names:

• chr9-99146083-T-G
• rs334353
• NM_004612.4:c.1131-402T>G

Variant summary

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

The NM_004612.4(TGFBR1):​c.1131-402T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 289,978 control chromosomes in the GnomAD database, including 10,292 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.26 (5219 hom., cov: 31)
  • Exomes 𝑓: 0.26 (5073 hom.)
• Consequence: TGFBR1 NM_004612.4 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -0.876
• Publications: 53 publications found

Genes affected

TGFBR1 (HGNC:11772): (transforming growth factor beta receptor 1) The protein encoded by this gene forms a heteromeric complex with type II TGF-beta receptors when bound to TGF-beta, transducing the TGF-beta signal from the cell surface to the cytoplasm. The encoded protein is a serine/threonine protein kinase. Mutations in this gene have been associated with Loeys-Dietz aortic aneurysm syndrome (LDAS). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

RNA5SP290 (HGNC:43190): (RNA, 5S ribosomal pseudogene 290)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004612.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBR1	NM_004612.4	MANE Select	c.1131-402T>G		intron	N/A	NP_004603.1
	TGFBR1	NM_001306210.2		c.1143-402T>G		intron	N/A	NP_001293139.1
	TGFBR1	NM_001407416.1		c.975-402T>G		intron	N/A	NP_001394345.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFBR1	ENST00000374994.9	TSL:1 MANE Select	c.1131-402T>G		intron	N/A	ENSP00000364133.4
	TGFBR1	ENST00000552516.5	TSL:1	c.1143-402T>G		intron	N/A	ENSP00000447297.1
	TGFBR1	ENST00000374990.6	TSL:1	c.900-402T>G		intron	N/A	ENSP00000364129.2

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39060 AN: 151892 Hom.: 5210 Cov.: 31

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.257

GnomAD4 exome AF: 0.262 AC: 36190 AN: 137966 Hom.: 5073 AF XY: 0.266 AC XY: 20183 AN XY: 75814

African (AFR) AF: 0.232 AC: 687 AN: 2966

American (AMR) AF: 0.254 AC: 1171 AN: 4612

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 737 AN: 3120

East Asian (EAS) AF: 0.447 AC: 2320 AN: 5188

South Asian (SAS) AF: 0.307 AC: 7726 AN: 25190

European-Finnish (FIN) AF: 0.196 AC: 1224 AN: 6234

Middle Eastern (MID) AF: 0.173 AC: 86 AN: 498

European-Non Finnish (NFE) AF: 0.247 AC: 20583 AN: 83454

Other (OTH) AF: 0.247 AC: 1656 AN: 6704

GnomAD4 genome AF: 0.257 AC: 39117 AN: 152012 Hom.: 5219 Cov.: 31 AF XY: 0.256 AC XY: 18995 AN XY: 74294

African (AFR) AF: 0.247 AC: 10223 AN: 41446

American (AMR) AF: 0.273 AC: 4164 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 821 AN: 3470

East Asian (EAS) AF: 0.432 AC: 2225 AN: 5154

South Asian (SAS) AF: 0.314 AC: 1511 AN: 4808

European-Finnish (FIN) AF: 0.200 AC: 2120 AN: 10580

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17263 AN: 67966

Other (OTH) AF: 0.260 AC: 548 AN: 2106

Alfa AF: 0.254 Hom.: 15606

Bravo AF: 0.259

Asia WGS AF: 0.372 AC: 1292 AN: 3478

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

Department of Ophthalmology and Visual Sciences Kyoto University

Significance: not provided

Review Status: no classification provided

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.68
DANN	Benign	0.51
PhyloP100		-0.88
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: rs334353; hg19: chr9-101908365;