rs4670322

Positions:

• chr2-33230675-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.1876+8524A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,162 control chromosomes in the GnomAD database, including 5,270 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 0.24 (5270 hom., cov: 32)
• Consequence: LTBP1 NM_206943.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0260

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTBP1	NM_206943.4	c.1876+8524A>G		intron_variant		ENST00000404816.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTBP1	ENST00000404816.7	c.1876+8524A>G		intron_variant		5	NM_206943.4	P3

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36247 AN: 152044 Hom.: 5268 Cov.: 32

Gnomad AFR AF: 0.0756

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.238 AC: 36248 AN: 152162 Hom.: 5270 Cov.: 32 AF XY: 0.240 AC XY: 17833 AN XY: 74386

Gnomad4 AFR AF: 0.0753

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.232

Alfa AF: 0.290 Hom.: 5013

Bravo AF: 0.231

Asia WGS AF: 0.168 AC: 581 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.51

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: rs4670322; hg19: chr2-33455742;