2-33135271-A-G

Variant names:

• chr2-33135271-A-G
• rs1545552
• NM_206943.4:c.1201+311A>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.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
• Publications: 22 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 (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206943.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTBP1	NM_206943.4	MANE Select	c.1201+311A>G		intron	N/A	NP_996826.3
	LTBP1	NM_001394905.1		c.1201+311A>G		intron	N/A	NP_001381834.1
	LTBP1	NM_000627.4		c.223+311A>G		intron	N/A	NP_000618.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTBP1	ENST00000404816.7	TSL:5 MANE Select	c.1201+311A>G		intron	N/A	ENSP00000386043.2
	LTBP1	ENST00000407925.5	TSL:1	c.223+311A>G		intron	N/A	ENSP00000384091.1
	LTBP1	ENST00000418533.6	TSL:1	c.223+311A>G		intron	N/A	ENSP00000393057.2

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

African (AFR) AF: 0.804 AC: 33357 AN: 41500

American (AMR) AF: 0.814 AC: 12439 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 2410 AN: 3470

East Asian (EAS) AF: 0.987 AC: 5118 AN: 5188

South Asian (SAS) AF: 0.827 AC: 3992 AN: 4830

European-Finnish (FIN) AF: 0.758 AC: 8022 AN: 10578

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.714 AC: 48570 AN: 67982

Other (OTH) AF: 0.763 AC: 1611 AN: 2112

Alfa AF: 0.734 Hom.: 128516

Bravo AF: 0.771

Asia WGS AF: 0.910 AC: 3166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.58
DANN	Benign	0.55
PhyloP100		-0.77
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: rs1545552; hg19: chr2-33360338;