rs334353

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr9-99146083-T-A
• chr9-99146083-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004612.4(TGFBR1):​c.1131-402T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000145 in 138,180 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: TGFBR1 NM_004612.4 intron
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR1	NM_004612.4	c.1131-402T>A		intron_variant	Intron 6 of 8	ENST00000374994.9	NP_004603.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR1	ENST00000374994.9	c.1131-402T>A		intron_variant	Intron 6 of 8	1	NM_004612.4	ENSP00000364133.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000145 AC: 2 AN: 138180 Hom.: 0 AF XY: 0.0000263 AC XY: 2 AN XY: 75946

African (AFR) AF: 0.00 AC: 0 AN: 2980

American (AMR) AF: 0.00 AC: 0 AN: 4612

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3124

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.0000396 AC: 1 AN: 25238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6240

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 498

European-Non Finnish (NFE) AF: 0.0000120 AC: 1 AN: 83572

Other (OTH) AF: 0.00 AC: 0 AN: 6712

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 15606

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.65
DANN	Benign	0.52
PhyloP100		-0.88

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;