2-33136358-A-G

Variant names:

• chr2-33136358-A-G
• rs6714546
• NM_206943.4:c.1201+1398A>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.1201+1398A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 152,210 control chromosomes in the GnomAD database, including 47,220 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 0.78 (47220 hom., cov: 33)
• Consequence: LTBP1 NM_206943.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.606
• Publications: 37 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=-0.65).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTBP1	NM_206943.4	c.1201+1398A>G		intron_variant	Intron 5 of 33	ENST00000404816.7	NP_996826.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTBP1	ENST00000404816.7	c.1201+1398A>G		intron_variant	Intron 5 of 33	5	NM_206943.4	ENSP00000386043.2

Frequencies

GnomAD3 genomes AF: 0.783 AC: 119095 AN: 152092 Hom.: 47175 Cov.: 33

Gnomad AFR AF: 0.859

Gnomad AMI AF: 0.865

Gnomad AMR AF: 0.825

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.988

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.759

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.774

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

GnomAD4 genome AF: 0.783 AC: 119196 AN: 152210 Hom.: 47220 Cov.: 33 AF XY: 0.788 AC XY: 58677 AN XY: 74422

African (AFR) AF: 0.859 AC: 35649 AN: 41518

American (AMR) AF: 0.825 AC: 12620 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 2411 AN: 3468

East Asian (EAS) AF: 0.988 AC: 5123 AN: 5186

South Asian (SAS) AF: 0.829 AC: 3997 AN: 4822

European-Finnish (FIN) AF: 0.759 AC: 8038 AN: 10588

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.716 AC: 48707 AN: 68016

Other (OTH) AF: 0.775 AC: 1636 AN: 2110

Alfa AF: 0.740 Hom.: 144205

Bravo AF: 0.791

Asia WGS AF: 0.915 AC: 3184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	12
DANN	Benign	0.84
PhyloP100		0.61
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: rs6714546; hg19: chr2-33361425;