rs2290447

Positions:

• chr2-33186799-A-G

Variant summary

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

The NM_206943.4(LTBP1):​c.1202-57A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0364 in 1,360,332 control chromosomes in the GnomAD database, including 2,232 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 0.078 (1000 hom., cov: 32)
  • Exomes 𝑓: 0.031 (1232 hom.)
• Consequence: LTBP1 NM_206943.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LTBP1	NM_206943.4	c.1202-57A>G		intron_variant		ENST00000404816.7	NP_996826.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LTBP1	ENST00000404816.7	c.1202-57A>G		intron_variant		5	NM_206943.4	ENSP00000386043.2

Frequencies

GnomAD3 genomes AF: 0.0781 AC: 11872 AN: 152082 Hom.: 986 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0443

Gnomad ASJ AF: 0.0573

Gnomad EAS AF: 0.0271

Gnomad SAS AF: 0.00726

Gnomad FIN AF: 0.0170

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.0248

Gnomad OTH AF: 0.0655

GnomAD4 exome AF: 0.0312 AC: 37660 AN: 1208132 Hom.: 1232 AF XY: 0.0296 AC XY: 17997 AN XY: 608960

Gnomad4 AFR exome AF: 0.218

Gnomad4 AMR exome AF: 0.0257

Gnomad4 ASJ exome AF: 0.0591

Gnomad4 EAS exome AF: 0.0441

Gnomad4 SAS exome AF: 0.00922

Gnomad4 FIN exome AF: 0.0132

Gnomad4 NFE exome AF: 0.0265

Gnomad4 OTH exome AF: 0.0408

GnomAD4 genome AF: 0.0783 AC: 11911 AN: 152200 Hom.: 1000 Cov.: 32 AF XY: 0.0750 AC XY: 5581 AN XY: 74422

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.0442

Gnomad4 ASJ AF: 0.0573

Gnomad4 EAS AF: 0.0272

Gnomad4 SAS AF: 0.00748

Gnomad4 FIN AF: 0.0170

Gnomad4 NFE AF: 0.0248

Gnomad4 OTH AF: 0.0643

Alfa AF: 0.0573 Hom.: 95

Bravo AF: 0.0878

Asia WGS AF: 0.0330 AC: 115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.3
DANN	Benign	0.48

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: rs2290447; hg19: chr2-33411866;