rs218195

Variant names:

• chr2-33120063-G-A
• rs218195
• NM_206943.4:c.1033+9312G>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.1033+9312G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.051 in 152,188 control chromosomes in the GnomAD database, including 262 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 0.051 (262 hom., cov: 32)
• Consequence: LTBP1 NM_206943.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTBP1	NM_206943.4	c.1033+9312G>A		intron_variant	Intron 4 of 33	ENST00000404816.7	NP_996826.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTBP1	ENST00000404816.7	c.1033+9312G>A		intron_variant	Intron 4 of 33	5	NM_206943.4	ENSP00000386043.2

Frequencies

GnomAD3 genomes AF: 0.0510 AC: 7753 AN: 152070 Hom.: 259 Cov.: 32

Gnomad AFR AF: 0.0288

Gnomad AMI AF: 0.0418

Gnomad AMR AF: 0.0459

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0183

Gnomad SAS AF: 0.0639

Gnomad FIN AF: 0.0495

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0640

Gnomad OTH AF: 0.0607

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

GnomAD4 genome AF: 0.0510 AC: 7762 AN: 152188 Hom.: 262 Cov.: 32 AF XY: 0.0494 AC XY: 3679 AN XY: 74410

African (AFR) AF: 0.0288 AC: 1197 AN: 41512

American (AMR) AF: 0.0458 AC: 701 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 397 AN: 3466

East Asian (EAS) AF: 0.0183 AC: 95 AN: 5186

South Asian (SAS) AF: 0.0642 AC: 309 AN: 4816

European-Finnish (FIN) AF: 0.0495 AC: 524 AN: 10582

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0640 AC: 4350 AN: 68008

Other (OTH) AF: 0.0615 AC: 130 AN: 2114

Alfa AF: 0.0579 Hom.: 590

Bravo AF: 0.0490

Asia WGS AF: 0.0350 AC: 120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.92
DANN	Benign	0.80
PhyloP100		-0.067
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs218195; hg19: chr2-33345130;