chr2-33165121-T-G

Variant names:

• chr2-33165121-T-G
• rs17012623
• NM_206943.4:c.1202-21735T>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.1202-21735T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0589 in 152,064 control chromosomes in the GnomAD database, including 390 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 0.059 (390 hom., cov: 32)
• Consequence: LTBP1 NM_206943.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71
• Publications: 0 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.204 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.1202-21735T>G		intron	N/A	NP_996826.3
	LTBP1	NM_001394905.1		c.1202-21735T>G		intron	N/A	NP_001381834.1
	LTBP1	NM_000627.4		c.224-21735T>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.1202-21735T>G		intron	N/A	ENSP00000386043.2
	LTBP1	ENST00000407925.5	TSL:1	c.224-21735T>G		intron	N/A	ENSP00000384091.1
	LTBP1	ENST00000418533.6	TSL:1	c.224-21735T>G		intron	N/A	ENSP00000393057.2

Frequencies

GnomAD3 genomes AF: 0.0589 AC: 8957 AN: 151946 Hom.: 391 Cov.: 32

Gnomad AFR AF: 0.0409

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.0537

Gnomad ASJ AF: 0.0845

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.0351

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0557

Gnomad OTH AF: 0.0718

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

GnomAD4 genome AF: 0.0589 AC: 8953 AN: 152064 Hom.: 390 Cov.: 32 AF XY: 0.0602 AC XY: 4474 AN XY: 74336

African (AFR) AF: 0.0410 AC: 1700 AN: 41484

American (AMR) AF: 0.0536 AC: 818 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0845 AC: 293 AN: 3468

East Asian (EAS) AF: 0.215 AC: 1107 AN: 5160

South Asian (SAS) AF: 0.141 AC: 680 AN: 4818

European-Finnish (FIN) AF: 0.0351 AC: 371 AN: 10572

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0557 AC: 3784 AN: 67980

Other (OTH) AF: 0.0711 AC: 150 AN: 2110

Alfa AF: 0.0610 Hom.: 393

Bravo AF: 0.0593

Asia WGS AF: 0.189 AC: 654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.0
DANN	Benign	0.63
PhyloP100		-1.7
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: rs17012623; hg19: chr2-33390188;