rs6543706

Variant names:

• chr2-33334643-G-T
• rs6543706
• NM_206943.4:c.3731-8195G>T

Variant summary

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

The NM_206943.4(LTBP1):​c.3731-8195G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,052 control chromosomes in the GnomAD database, including 3,442 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 0.17 (3442 hom., cov: 31)
• Consequence: LTBP1 NM_206943.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.881
• 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206943.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTBP1	NM_206943.4	MANE Select	c.3731-8195G>T		intron	N/A	NP_996826.3	Q14766-1
	LTBP1	NM_001394905.1		c.3572-8195G>T		intron	N/A	NP_001381834.1
	LTBP1	NM_000627.4		c.2753-8195G>T		intron	N/A	NP_000618.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTBP1	ENST00000404816.7	TSL:5 MANE Select	c.3731-8195G>T		intron	N/A	ENSP00000386043.2	Q14766-1
	LTBP1	ENST00000407925.5	TSL:1	c.2753-8195G>T		intron	N/A	ENSP00000384091.1	Q14766-2
	LTBP1	ENST00000418533.6	TSL:1	c.2753-12724G>T		intron	N/A	ENSP00000393057.2	E7EV71

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25862 AN: 151934 Hom.: 3421 Cov.: 31

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.0448

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0833

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.170 AC: 25914 AN: 152052 Hom.: 3442 Cov.: 31 AF XY: 0.169 AC XY: 12543 AN XY: 74354

African (AFR) AF: 0.365 AC: 15121 AN: 41424

American (AMR) AF: 0.142 AC: 2171 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 410 AN: 3470

East Asian (EAS) AF: 0.191 AC: 987 AN: 5166

South Asian (SAS) AF: 0.142 AC: 685 AN: 4816

European-Finnish (FIN) AF: 0.0448 AC: 475 AN: 10592

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.0833 AC: 5662 AN: 67984

Other (OTH) AF: 0.147 AC: 310 AN: 2112

Alfa AF: 0.120 Hom.: 789

Bravo AF: 0.187

Asia WGS AF: 0.185 AC: 642 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.8
DANN	Benign	0.76
PhyloP100		0.88
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: rs6543706; hg19: chr2-33559710;