chr2-33241416-A-G

Variant names:

• chr2-33241416-A-G
• rs12468769
• NM_206943.4:c.1877-2246A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_206943.4(LTBP1):​c.1877-2246A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 152,094 control chromosomes in the GnomAD database, including 25,062 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 0.56 (25062 hom., cov: 33)
• Consequence: LTBP1 NM_206943.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920
• Publications: 4 publications found

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]

LTBP1 Gene-Disease associations (from GenCC):

• cutis laxa, autosomal recessive, type 2E

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTBP1	NM_206943.4	c.1877-2246A>G		intron_variant	Intron 9 of 33	ENST00000404816.7	NP_996826.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTBP1	ENST00000404816.7	c.1877-2246A>G		intron_variant	Intron 9 of 33	5	NM_206943.4	ENSP00000386043.2

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85746 AN: 151976 Hom.: 25035 Cov.: 33

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.534

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

GnomAD4 genome AF: 0.564 AC: 85830 AN: 152094 Hom.: 25062 Cov.: 33 AF XY: 0.564 AC XY: 41923 AN XY: 74360

African (AFR) AF: 0.437 AC: 18108 AN: 41464

American (AMR) AF: 0.560 AC: 8556 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1937 AN: 3470

East Asian (EAS) AF: 0.376 AC: 1937 AN: 5158

South Asian (SAS) AF: 0.406 AC: 1959 AN: 4822

European-Finnish (FIN) AF: 0.740 AC: 7837 AN: 10592

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.642 AC: 43672 AN: 67988

Other (OTH) AF: 0.535 AC: 1129 AN: 2112

Alfa AF: 0.612 Hom.: 68543

Bravo AF: 0.548

Asia WGS AF: 0.394 AC: 1370 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	4.2
DANN	Benign	0.54
PhyloP100		0.092
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12468769; hg19: chr2-33466483;