2-33385844-G-A

Variant names:

• chr2-33385844-G-A
• rs11885449
• NM_206943.4:c.4712-3340G>A

Variant summary

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

The NM_206943.4(LTBP1):​c.4712-3340G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 152,064 control chromosomes in the GnomAD database, including 14,232 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 0.40 (14232 hom., cov: 32)
• Consequence: LTBP1 NM_206943.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.610
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.647 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.4712-3340G>A		intron	N/A	NP_996826.3
	LTBP1	NM_001394905.1		c.4553-3340G>A		intron	N/A	NP_001381834.1
	LTBP1	NM_000627.4		c.3734-3340G>A		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.4712-3340G>A		intron	N/A	ENSP00000386043.2
	LTBP1	ENST00000407925.5	TSL:1	c.3734-3340G>A		intron	N/A	ENSP00000384091.1
	LTBP1	ENST00000418533.6	TSL:1	c.3608-3340G>A		intron	N/A	ENSP00000393057.2

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60824 AN: 151946 Hom.: 14193 Cov.: 32

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.401 AC: 60921 AN: 152064 Hom.: 14232 Cov.: 32 AF XY: 0.394 AC XY: 29262 AN XY: 74324

African (AFR) AF: 0.653 AC: 27083 AN: 41464

American (AMR) AF: 0.310 AC: 4743 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1135 AN: 3466

East Asian (EAS) AF: 0.216 AC: 1117 AN: 5164

South Asian (SAS) AF: 0.294 AC: 1417 AN: 4814

European-Finnish (FIN) AF: 0.274 AC: 2894 AN: 10570

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21485 AN: 67984

Other (OTH) AF: 0.375 AC: 791 AN: 2110

Alfa AF: 0.333 Hom.: 5018

Bravo AF: 0.416

Asia WGS AF: 0.299 AC: 1043 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.55
PhyloP100		0.61
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: rs11885449; hg19: chr2-33610911;