rs11904654

Positions:

• chr2-33109632-T-G

Variant summary

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

The NM_206943.4(LTBP1):​c.864-950T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,122 control chromosomes in the GnomAD database, including 3,678 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 0.20 (3678 hom., cov: 33)
• Consequence: LTBP1 NM_206943.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.741

Genes affected

LTBP1 (HGNC:6714): (latent transforming growth factor beta binding protein 1) The protein encoded by this gene belongs to the family of latent TGF-beta binding proteins (LTBPs). The secretion and activation of TGF-betas is regulated by their association with latency-associated proteins and with latent TGF-beta binding proteins. The product of this gene targets latent complexes of transforming growth factor beta to the extracellular matrix, where the latent cytokine is subsequently activated by several different mechanisms. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LTBP1	NM_206943.4	c.864-950T>G		intron_variant		ENST00000404816.7	NP_996826.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LTBP1	ENST00000404816.7	c.864-950T>G		intron_variant		5	NM_206943.4	ENSP00000386043.2

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30631 AN: 152004 Hom.: 3670 Cov.: 33

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.202 AC: 30676 AN: 152122 Hom.: 3678 Cov.: 33 AF XY: 0.205 AC XY: 15215 AN XY: 74372

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.200

Alfa AF: 0.155 Hom.: 2833

Bravo AF: 0.219

Asia WGS AF: 0.300 AC: 1039 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.6
DANN	Benign	0.67

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: rs11904654; hg19: chr2-33334699;