2-33135271-A-G

Position:

• chr2-33135271-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.1201+311A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 152,156 control chromosomes in the GnomAD database, including 45,020 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 0.77 (45020 hom., cov: 32)
• Consequence: LTBP1 NM_206943.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.773

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LTBP1	NM_206943.4	c.1201+311A>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.1201+311A>G		intron_variant		5	NM_206943.4	ENSP00000386043.2

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116437 AN: 152038 Hom.: 44982 Cov.: 32

Gnomad AFR AF: 0.804

Gnomad AMI AF: 0.865

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.758

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.762

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

GnomAD4 genome AF: 0.766 AC: 116533 AN: 152156 Hom.: 45020 Cov.: 32 AF XY: 0.771 AC XY: 57351 AN XY: 74394

Gnomad4 AFR AF: 0.804

Gnomad4 AMR AF: 0.814

Gnomad4 ASJ AF: 0.695

Gnomad4 EAS AF: 0.987

Gnomad4 SAS AF: 0.827

Gnomad4 FIN AF: 0.758

Gnomad4 NFE AF: 0.714

Gnomad4 OTH AF: 0.763

Alfa AF: 0.724 Hom.: 51348

Bravo AF: 0.771

Asia WGS AF: 0.910 AC: 3166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.58
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: rs1545552; hg19: chr2-33360338;