chr2-33272268-A-G

Variant names:

• chr2-33272268-A-G
• rs817529
• NM_206943.4:c.2618-1388A>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.2618-1388A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 152,102 control chromosomes in the GnomAD database, including 10,681 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 0.36 (10681 hom., cov: 32)
• Consequence: LTBP1 NM_206943.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.210
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.41 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.2618-1388A>G		intron	N/A	NP_996826.3
	LTBP1	NM_001394905.1		c.2459-1388A>G		intron	N/A	NP_001381834.1
	LTBP1	NM_000627.4		c.1640-1388A>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.2618-1388A>G		intron	N/A	ENSP00000386043.2
	LTBP1	ENST00000407925.5	TSL:1	c.1640-1388A>G		intron	N/A	ENSP00000384091.1
	LTBP1	ENST00000418533.6	TSL:1	c.1640-1388A>G		intron	N/A	ENSP00000393057.2

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54542 AN: 151984 Hom.: 10677 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.0856

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.359 AC: 54563 AN: 152102 Hom.: 10681 Cov.: 32 AF XY: 0.360 AC XY: 26802 AN XY: 74368

African (AFR) AF: 0.256 AC: 10618 AN: 41508

American (AMR) AF: 0.419 AC: 6399 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1006 AN: 3462

East Asian (EAS) AF: 0.0860 AC: 445 AN: 5176

South Asian (SAS) AF: 0.363 AC: 1752 AN: 4828

European-Finnish (FIN) AF: 0.480 AC: 5067 AN: 10558

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.411 AC: 27959 AN: 67984

Other (OTH) AF: 0.336 AC: 708 AN: 2106

Alfa AF: 0.386 Hom.: 32904

Bravo AF: 0.349

Asia WGS AF: 0.234 AC: 813 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.85
DANN	Benign	0.43
PhyloP100		-0.21
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: rs817529; hg19: chr2-33497335;