rs11885449

Positions:

• chr2-33385844-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.4712-3340G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 152,064 control chromosomes in the GnomAD database, including 14,232 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 0.40 (14232 hom., cov: 32)
• Consequence: LTBP1 NM_206943.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.610

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTBP1	NM_206943.4	c.4712-3340G>A		intron_variant		ENST00000404816.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTBP1	ENST00000404816.7	c.4712-3340G>A		intron_variant		5	NM_206943.4	P3

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60824 AN: 151946 Hom.: 14193 Cov.: 32

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.401 AC: 60921 AN: 152064 Hom.: 14232 Cov.: 32 AF XY: 0.394 AC XY: 29262 AN XY: 74324

Gnomad4 AFR AF: 0.653

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.375

Alfa AF: 0.334 Hom.: 4574

Bravo AF: 0.416

Asia WGS AF: 0.299 AC: 1043 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.55

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: rs11885449; hg19: chr2-33610911;