rs3769528

Variant names:

• chr2-33246125-A-G
• rs3769528
• NM_206943.4:c.1999+2341A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_206943.4(LTBP1):​c.1999+2341A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0136 in 152,346 control chromosomes in the GnomAD database, including 106 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 0.014 (106 hom., cov: 33)
• Consequence: LTBP1 NM_206943.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• Publications: 9 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTBP1	NM_206943.4	c.1999+2341A>G		intron_variant	Intron 10 of 33	ENST00000404816.7	NP_996826.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTBP1	ENST00000404816.7	c.1999+2341A>G		intron_variant	Intron 10 of 33	5	NM_206943.4	ENSP00000386043.2

Frequencies

GnomAD3 genomes AF: 0.0136 AC: 2073 AN: 152228 Hom.: 106 Cov.: 33

Gnomad AFR AF: 0.00916

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0149

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.0972

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00119

Gnomad OTH AF: 0.0129

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

GnomAD4 genome AF: 0.0136 AC: 2072 AN: 152346 Hom.: 106 Cov.: 33 AF XY: 0.0161 AC XY: 1202 AN XY: 74502

African (AFR) AF: 0.00923 AC: 384 AN: 41586

American (AMR) AF: 0.0148 AC: 227 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.167 AC: 862 AN: 5174

South Asian (SAS) AF: 0.0969 AC: 468 AN: 4830

European-Finnish (FIN) AF: 0.00141 AC: 15 AN: 10624

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00119 AC: 81 AN: 68036

Other (OTH) AF: 0.0132 AC: 28 AN: 2114

Alfa AF: 0.00731 Hom.: 110

Bravo AF: 0.0146

Asia WGS AF: 0.113 AC: 391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	14
DANN	Benign	0.68
PhyloP100		1.1
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: rs3769528; hg19: chr2-33471192;