2-33316635-A-G

Variant names:

• chr2-33316635-A-G
• rs723042
• NM_206943.4:c.3730+1366A>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.3730+1366A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 152,044 control chromosomes in the GnomAD database, including 36,365 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 0.67 (36365 hom., cov: 31)
• Consequence: LTBP1 NM_206943.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.348
• Publications: 5 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTBP1	NM_206943.4	c.3730+1366A>G		intron_variant	Intron 24 of 33	ENST00000404816.7	NP_996826.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTBP1	ENST00000404816.7	c.3730+1366A>G		intron_variant	Intron 24 of 33	5	NM_206943.4	ENSP00000386043.2

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102322 AN: 151926 Hom.: 36342 Cov.: 31

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.933

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.836

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.788

Gnomad OTH AF: 0.642

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

GnomAD4 genome AF: 0.673 AC: 102388 AN: 152044 Hom.: 36365 Cov.: 31 AF XY: 0.677 AC XY: 50285 AN XY: 74330

African (AFR) AF: 0.445 AC: 18422 AN: 41444

American (AMR) AF: 0.713 AC: 10885 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 2370 AN: 3466

East Asian (EAS) AF: 0.528 AC: 2722 AN: 5156

South Asian (SAS) AF: 0.665 AC: 3205 AN: 4818

European-Finnish (FIN) AF: 0.836 AC: 8844 AN: 10576

Middle Eastern (MID) AF: 0.551 AC: 161 AN: 292

European-Non Finnish (NFE) AF: 0.788 AC: 53567 AN: 67990

Other (OTH) AF: 0.644 AC: 1361 AN: 2114

Alfa AF: 0.746 Hom.: 190418

Bravo AF: 0.656

Asia WGS AF: 0.606 AC: 2110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.8
DANN	Benign	0.43
PhyloP100		0.35
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: rs723042; hg19: chr2-33541702;