rs6706122

Positions:

• chr2-33222025-C-A
• chr2-33222025-C-G

Variant summary

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

The NM_206943.4(LTBP1):​c.1805-55C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0374 in 1,273,900 control chromosomes in the GnomAD database, including 2,231 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 (1022 hom., cov: 33)
  • Exomes 𝑓: 0.032 (1209 hom.)
• Consequence: LTBP1 NM_206943.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LTBP1	NM_206943.4	c.1805-55C>A		intron_variant		ENST00000404816.7	NP_996826.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LTBP1	ENST00000404816.7	c.1805-55C>A		intron_variant		5	NM_206943.4	ENSP00000386043	P3

Frequencies

GnomAD3 genomes AF: 0.0776 AC: 11806 AN: 152070 Hom.: 1010 Cov.: 33

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.0425

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.0266

Gnomad SAS AF: 0.00746

Gnomad FIN AF: 0.0170

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0249

Gnomad OTH AF: 0.0746

GnomAD4 exome AF: 0.0319 AC: 35805 AN: 1121712 Hom.: 1209 AF XY: 0.0302 AC XY: 17313 AN XY: 573634

Gnomad4 AFR exome AF: 0.223

Gnomad4 AMR exome AF: 0.0251

Gnomad4 ASJ exome AF: 0.0590

Gnomad4 EAS exome AF: 0.0436

Gnomad4 SAS exome AF: 0.00885

Gnomad4 FIN exome AF: 0.0133

Gnomad4 NFE exome AF: 0.0273

Gnomad4 OTH exome AF: 0.0413

GnomAD4 genome AF: 0.0779 AC: 11854 AN: 152188 Hom.: 1022 Cov.: 33 AF XY: 0.0750 AC XY: 5580 AN XY: 74406

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.0425

Gnomad4 ASJ AF: 0.0565

Gnomad4 EAS AF: 0.0266

Gnomad4 SAS AF: 0.00767

Gnomad4 FIN AF: 0.0170

Gnomad4 NFE AF: 0.0249

Gnomad4 OTH AF: 0.0734

Alfa AF: 0.0313 Hom.: 266

Bravo AF: 0.0864

Asia WGS AF: 0.0340 AC: 119 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.3
DANN	Benign	0.25

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: rs6706122; hg19: chr2-33447092;