rs1902030

Positions:

• chr2-33095524-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_206943.4(LTBP1):​c.864-15058G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0655 in 152,064 control chromosomes in the GnomAD database, including 828 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 0.066 (828 hom., cov: 32)
• Consequence: LTBP1 NM_206943.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LTBP1	NM_206943.4	c.864-15058G>A		intron_variant		ENST00000404816.7	NP_996826.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LTBP1	ENST00000404816.7	c.864-15058G>A		intron_variant		5	NM_206943.4	ENSP00000386043	P3

Frequencies

GnomAD3 genomes AF: 0.0655 AC: 9957 AN: 151946 Hom.: 822 Cov.: 32

Gnomad AFR AF: 0.0276

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.0291

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0689

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0374

Gnomad OTH AF: 0.0780

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

GnomAD4 genome AF: 0.0655 AC: 9966 AN: 152064 Hom.: 828 Cov.: 32 AF XY: 0.0721 AC XY: 5356 AN XY: 74328

Gnomad4 AFR AF: 0.0275

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.0291

Gnomad4 EAS AF: 0.412

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.0689

Gnomad4 NFE AF: 0.0374

Gnomad4 OTH AF: 0.0791

Alfa AF: 0.0467 Hom.: 58

Bravo AF: 0.0747

Asia WGS AF: 0.221 AC: 768 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.8
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs1902030; hg19: chr2-33320591;