rs6478972

chr9-99106996-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004612.4(TGFBR1):c.97+1694G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,002 control chromosomes in the GnomAD database, including 4,835 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 0.25 (4835 hom., cov: 33)
• Consequence: TGFBR1 NM_004612.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFBR1	NM_004612.4	c.97+1694G>A		intron_variant		ENST00000374994.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFBR1	ENST00000374994.9	c.97+1694G>A		intron_variant		1	NM_004612.4	P4

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37228 AN: 151882 Hom.: 4818 Cov.: 33

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.239

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.245 AC: 37290 AN: 152002 Hom.: 4835 Cov.: 33 AF XY: 0.243 AC XY: 18040 AN XY: 74320

Gnomad4 AFR AF: 0.297

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.463

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.238

Alfa AF: 0.234 Hom.: 704

Bravo AF: 0.253

Asia WGS AF: 0.361 AC: 1254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.8
Dann	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs6478972; hg19: chr9-101869278;