rs571184242

Variant names:

• chr2-32947787-C-A
• rs571184242
• NM_206943.4:c.463C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-32947787-C-A
• chr2-32947787-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_206943.4(LTBP1):​c.463C>A​(p.Leu155Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000941 in 1,487,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: LTBP1 NM_206943.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.27
• 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11395535).

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.463C>A	p.Leu155Met	missense	Exon 1 of 34	NP_996826.3	Q14766-1
	LTBP1	NM_001394905.1		c.463C>A	p.Leu155Met	missense	Exon 1 of 34	NP_001381834.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTBP1	ENST00000404816.7	TSL:5 MANE Select	c.463C>A	p.Leu155Met	missense	Exon 1 of 34	ENSP00000386043.2	Q14766-1
	LTBP1	ENST00000929169.1		c.463C>A	p.Leu155Met	missense	Exon 1 of 34	ENSP00000599228.1
	LTBP1	ENST00000954823.1		c.463C>A	p.Leu155Met	missense	Exon 1 of 34	ENSP00000624882.1

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152050 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000686 AC: 1 AN: 145690 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000483

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000374 AC: 5 AN: 1335166 Hom.: 0 Cov.: 33 AF XY: 0.00000151 AC XY: 1 AN XY: 661522

African (AFR) AF: 0.00 AC: 0 AN: 27648

American (AMR) AF: 0.0000652 AC: 2 AN: 30688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22266

East Asian (EAS) AF: 0.00 AC: 0 AN: 30884

South Asian (SAS) AF: 0.00 AC: 0 AN: 68874

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5220

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1047142

Other (OTH) AF: 0.0000555 AC: 3 AN: 54074

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152158 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74382

African (AFR) AF: 0.0000241 AC: 1 AN: 41554

American (AMR) AF: 0.000523 AC: 8 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67962

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.0000223 Hom.: 0

Bravo AF: 0.000144

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.10	T
Eigen	Benign	0.022
Eigen_PC	Benign	0.059
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.46	T
M_CAP	Pathogenic	0.52	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	0.81	L
PhyloP100		2.3
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.25
Sift	Benign	0.10	T
Sift4G	Benign	0.10	T
Vest4		0.28
MutPred		0.094		Gain of MoRF binding (P = 0.0697)
MVP		0.19
MPC		0.15
ClinPred		0.29	T
GERP RS		2.7
Varity_R		0.12
gMVP		0.086
Mutation Taster		=100/0	polymorphism

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: rs571184242; hg19: chr2-33172854;