rs4670322

Variant names:

• chr2-33230675-A-G
• rs4670322
• NM_206943.4:c.1876+8524A>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.1876+8524A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,162 control chromosomes in the GnomAD database, including 5,270 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 0.24 (5270 hom., cov: 32)
• Consequence: LTBP1 NM_206943.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0260
• 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.317 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.1876+8524A>G		intron	N/A	NP_996826.3	Q14766-1
	LTBP1	NM_001394905.1		c.1876+8524A>G		intron	N/A	NP_001381834.1
	LTBP1	NM_000627.4		c.898+8524A>G		intron	N/A	NP_000618.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTBP1	ENST00000404816.7	TSL:5 MANE Select	c.1876+8524A>G		intron	N/A	ENSP00000386043.2	Q14766-1
	LTBP1	ENST00000407925.5	TSL:1	c.898+8524A>G		intron	N/A	ENSP00000384091.1	Q14766-2
	LTBP1	ENST00000418533.6	TSL:1	c.898+8524A>G		intron	N/A	ENSP00000393057.2	E7EV71

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36247 AN: 152044 Hom.: 5268 Cov.: 32

Gnomad AFR AF: 0.0756

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.238 AC: 36248 AN: 152162 Hom.: 5270 Cov.: 32 AF XY: 0.240 AC XY: 17833 AN XY: 74386

African (AFR) AF: 0.0753 AC: 3129 AN: 41548

American (AMR) AF: 0.325 AC: 4965 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 891 AN: 3464

East Asian (EAS) AF: 0.160 AC: 830 AN: 5186

South Asian (SAS) AF: 0.217 AC: 1044 AN: 4816

European-Finnish (FIN) AF: 0.318 AC: 3358 AN: 10562

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21157 AN: 67978

Other (OTH) AF: 0.232 AC: 490 AN: 2110

Alfa AF: 0.281 Hom.: 6329

Bravo AF: 0.231

Asia WGS AF: 0.168 AC: 581 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.51
PhyloP100		-0.026
Mutation Taster		=99/1	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: rs4670322; hg19: chr2-33455742;