rs11904654

Variant names:

• chr2-33109632-T-G
• rs11904654
• NM_206943.4:c.864-950T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

LTBP1 Gene-Disease associations (from GenCC):

• cutis laxa, autosomal recessive, type 2E

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LTBP1	NM_206943.4	c.864-950T>G		intron_variant	Intron 3 of 33	ENST00000404816.7	NP_996826.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTBP1	ENST00000404816.7	c.864-950T>G		intron_variant	Intron 3 of 33	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

African (AFR) AF: 0.268 AC: 11096 AN: 41462

American (AMR) AF: 0.273 AC: 4176 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 520 AN: 3472

East Asian (EAS) AF: 0.451 AC: 2334 AN: 5172

South Asian (SAS) AF: 0.214 AC: 1029 AN: 4818

European-Finnish (FIN) AF: 0.123 AC: 1305 AN: 10588

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9639 AN: 68000

Other (OTH) AF: 0.200 AC: 423 AN: 2114

Alfa AF: 0.162 Hom.: 4814

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
PhyloP100		0.74
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: rs11904654; hg19: chr2-33334699;