2-33196832-C-A

Variant names:

• chr2-33196832-C-A
• rs9308932
• NM_206943.4:c.1701+7981C>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.1701+7981C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0807 in 152,006 control chromosomes in the GnomAD database, including 1,062 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 0.081 (1062 hom., cov: 32)
• Consequence: LTBP1 NM_206943.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• 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: 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.217 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.1701+7981C>A		intron	N/A	NP_996826.3	Q14766-1
	LTBP1	NM_001394905.1		c.1701+7981C>A		intron	N/A	NP_001381834.1
	LTBP1	NM_000627.4		c.723+7981C>A		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.1701+7981C>A		intron	N/A	ENSP00000386043.2	Q14766-1
	LTBP1	ENST00000407925.5	TSL:1	c.723+7981C>A		intron	N/A	ENSP00000384091.1	Q14766-2
	LTBP1	ENST00000418533.6	TSL:1	c.723+7981C>A		intron	N/A	ENSP00000393057.2	E7EV71

Frequencies

GnomAD3 genomes AF: 0.0805 AC: 12221 AN: 151888 Hom.: 1051 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0451

Gnomad ASJ AF: 0.0573

Gnomad EAS AF: 0.0267

Gnomad SAS AF: 0.00726

Gnomad FIN AF: 0.0168

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0247

Gnomad OTH AF: 0.0668

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

GnomAD4 genome AF: 0.0807 AC: 12261 AN: 152006 Hom.: 1062 Cov.: 32 AF XY: 0.0773 AC XY: 5745 AN XY: 74310

African (AFR) AF: 0.221 AC: 9156 AN: 41392

American (AMR) AF: 0.0450 AC: 688 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0573 AC: 199 AN: 3472

East Asian (EAS) AF: 0.0267 AC: 138 AN: 5166

South Asian (SAS) AF: 0.00748 AC: 36 AN: 4816

European-Finnish (FIN) AF: 0.0168 AC: 178 AN: 10574

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0247 AC: 1681 AN: 68004

Other (OTH) AF: 0.0657 AC: 138 AN: 2102

Alfa AF: 0.0461 Hom.: 86

Bravo AF: 0.0908

Asia WGS AF: 0.0310 AC: 108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.6
DANN	Benign	0.38
PhyloP100		1.0
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: rs9308932; hg19: chr2-33421899;