2-33017488-C-T

Variant names:

• chr2-33017488-C-T
• rs219186
• NM_206943.4:c.566-3421C>T

Variant summary

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

The NM_206943.4(LTBP1):​c.566-3421C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.725 in 152,092 control chromosomes in the GnomAD database, including 42,211 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 0.72 (42211 hom., cov: 32)
• Consequence: LTBP1 NM_206943.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.737
• Publications: 2 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTBP1	NM_206943.4	c.566-3421C>T		intron_variant	Intron 2 of 33	ENST00000404816.7	NP_996826.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTBP1	ENST00000404816.7	c.566-3421C>T		intron_variant	Intron 2 of 33	5	NM_206943.4	ENSP00000386043.2

Frequencies

GnomAD3 genomes AF: 0.725 AC: 110165 AN: 151974 Hom.: 42189 Cov.: 32

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.903

Gnomad AMR AF: 0.796

Gnomad ASJ AF: 0.786

Gnomad EAS AF: 0.984

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.835

Gnomad OTH AF: 0.752

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

GnomAD4 genome AF: 0.725 AC: 110246 AN: 152092 Hom.: 42211 Cov.: 32 AF XY: 0.727 AC XY: 54054 AN XY: 74358

African (AFR) AF: 0.452 AC: 18720 AN: 41422

American (AMR) AF: 0.795 AC: 12167 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.786 AC: 2730 AN: 3472

East Asian (EAS) AF: 0.984 AC: 5097 AN: 5178

South Asian (SAS) AF: 0.767 AC: 3698 AN: 4820

European-Finnish (FIN) AF: 0.796 AC: 8427 AN: 10586

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.835 AC: 56776 AN: 68006

Other (OTH) AF: 0.753 AC: 1587 AN: 2108

Alfa AF: 0.788 Hom.: 27138

Bravo AF: 0.716

Asia WGS AF: 0.844 AC: 2937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.8
DANN	Benign	0.68
PhyloP100		0.74
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: rs219186; hg19: chr2-33242555;