rs397515430

Variant names:

• chr19-40608315-C-G
• NM_001042545.2:c.1252C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-40608315-C-G
• chr19-40608315-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001042545.2(LTBP4):​c.1252C>G​(p.Arg418Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,422 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LTBP4 NM_001042545.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89

Genes affected

LTBP4 (HGNC:6717): (latent transforming growth factor beta binding protein 4) The protein encoded by this gene binds transforming growth factor beta (TGFB) as it is secreted and targeted to the extracellular matrix. TGFB is biologically latent after secretion and insertion into the extracellular matrix, and sheds TGFB and other proteins upon activation. Defects in this gene may be a cause of cutis laxa and severe pulmonary, gastrointestinal, and urinary abnormalities. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTBP4	NM_001042545.2	c.1252C>G	p.Arg418Gly	missense_variant	Exon 8 of 30	ENST00000396819.8	NP_001036010.1
LTBP4	NM_001042544.1	c.1453C>G	p.Arg485Gly	missense_variant	Exon 11 of 33		NP_001036009.1
LTBP4	NM_003573.2	c.1342C>G	p.Arg448Gly	missense_variant	Exon 11 of 33		NP_003564.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTBP4	ENST00000396819.8	c.1252C>G	p.Arg418Gly	missense_variant	Exon 8 of 30	1	NM_001042545.2	ENSP00000380031.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461422 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726992

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.093	T;T;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.85	T;T;T
M_CAP	Benign	0.059	D
MetaRNN	Uncertain	0.69	D;D;D
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Benign	2.0	.;M;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Uncertain	0.38
Sift	Benign	0.12	T;T;T
Sift4G	Benign	0.38	T;T;T
Polyphen		0.99	.;D;.
Vest4		0.76
MutPred		0.48		.;Gain of catalytic residue at V486 (P = 0.0231);.;
MVP		0.59
MPC		1.3
ClinPred		0.86	D
GERP RS		5.3
Varity_R		0.28
gMVP		0.59

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-41114221;