rs17012623

chr2-33165121-T-G

Variant summary

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

The NM_206943.4(LTBP1):c.1202-21735T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0589 in 152,064 control chromosomes in the GnomAD database, including 390 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 0.059 (390 hom., cov: 32)
• Consequence: LTBP1 NM_206943.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTBP1	NM_206943.4	c.1202-21735T>G		intron_variant		ENST00000404816.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTBP1	ENST00000404816.7	c.1202-21735T>G		intron_variant		5	NM_206943.4	P3

Frequencies

GnomAD3 genomes AF: 0.0589 AC: 8957 AN: 151946 Hom.: 391 Cov.: 32

Gnomad AFR AF: 0.0409

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.0537

Gnomad ASJ AF: 0.0845

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.0351

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0557

Gnomad OTH AF: 0.0718

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

GnomAD4 genome AF: 0.0589 AC: 8953 AN: 152064 Hom.: 390 Cov.: 32 AF XY: 0.0602 AC XY: 4474 AN XY: 74336

Gnomad4 AFR AF: 0.0410

Gnomad4 AMR AF: 0.0536

Gnomad4 ASJ AF: 0.0845

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.0351

Gnomad4 NFE AF: 0.0557

Gnomad4 OTH AF: 0.0711

Alfa AF: 0.0587 Hom.: 207

Bravo AF: 0.0593

Asia WGS AF: 0.189 AC: 654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.0
Dann	Benign	0.63

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: rs17012623; hg19: chr2-33390188;