rs7582215

Variant names:

• chr2-33003100-G-A
• rs7582215
• NM_206943.4:c.566-17809G>A

Variant summary

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

The NM_206943.4(LTBP1):​c.566-17809G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 152,116 control chromosomes in the GnomAD database, including 10,377 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 0.36 (10377 hom., cov: 33)
• Consequence: LTBP1 NM_206943.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 4 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTBP1	NM_206943.4	c.566-17809G>A		intron_variant	Intron 2 of 33	ENST00000404816.7	NP_996826.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTBP1	ENST00000404816.7	c.566-17809G>A		intron_variant	Intron 2 of 33	5	NM_206943.4	ENSP00000386043.2

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54861 AN: 151998 Hom.: 10371 Cov.: 33

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.680

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.361 AC: 54891 AN: 152116 Hom.: 10377 Cov.: 33 AF XY: 0.367 AC XY: 27311 AN XY: 74380

African (AFR) AF: 0.269 AC: 11171 AN: 41498

American (AMR) AF: 0.368 AC: 5614 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1598 AN: 3472

East Asian (EAS) AF: 0.679 AC: 3513 AN: 5170

South Asian (SAS) AF: 0.434 AC: 2092 AN: 4818

European-Finnish (FIN) AF: 0.371 AC: 3924 AN: 10580

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.378 AC: 25693 AN: 67984

Other (OTH) AF: 0.402 AC: 849 AN: 2114

Alfa AF: 0.372 Hom.: 6421

Bravo AF: 0.359

Asia WGS AF: 0.561 AC: 1951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0030
DANN	Benign	0.76
PhyloP100		-1.5
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: rs7582215; hg19: chr2-33228167;