2-33012456-T-C

Variant names:

• chr2-33012456-T-C
• rs4952281
• NM_206943.4:c.566-8453T>C

Variant summary

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

The NM_206943.4(LTBP1):​c.566-8453T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 152,210 control chromosomes in the GnomAD database, including 12,003 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 0.37 (12003 hom., cov: 33)
• Consequence: LTBP1 NM_206943.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.351
• Publications: 3 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.937 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTBP1	NM_206943.4	MANE Select	c.566-8453T>C		intron	N/A	NP_996826.3
	LTBP1	NM_001394905.1		c.566-8453T>C		intron	N/A	NP_001381834.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTBP1	ENST00000404816.7	TSL:5 MANE Select	c.566-8453T>C		intron	N/A	ENSP00000386043.2
	LTBP1	ENST00000929169.1		c.566-8453T>C		intron	N/A	ENSP00000599228.1
	LTBP1	ENST00000954823.1		c.566-8453T>C		intron	N/A	ENSP00000624882.1

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55845 AN: 152092 Hom.: 11991 Cov.: 33

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.960

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.367 AC: 55892 AN: 152210 Hom.: 12003 Cov.: 33 AF XY: 0.375 AC XY: 27919 AN XY: 74410

African (AFR) AF: 0.213 AC: 8867 AN: 41552

American (AMR) AF: 0.509 AC: 7792 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1515 AN: 3470

East Asian (EAS) AF: 0.960 AC: 4967 AN: 5176

South Asian (SAS) AF: 0.448 AC: 2160 AN: 4820

European-Finnish (FIN) AF: 0.338 AC: 3579 AN: 10600

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.379 AC: 25758 AN: 67980

Other (OTH) AF: 0.398 AC: 841 AN: 2112

Alfa AF: 0.375 Hom.: 9433

Bravo AF: 0.380

Asia WGS AF: 0.669 AC: 2325 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.7
DANN	Benign	0.60
PhyloP100		0.35
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: rs4952281; hg19: chr2-33237523;