rs33937741

Variant names:

• chr19-40610549-C-A
• rs33937741
• NM_001042545.2:c.1702C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-40610549-C-A
• chr19-40610549-C-G
• chr19-40610549-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001042545.2(LTBP4):​c.1702C>A​(p.Arg568Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R568G) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LTBP4 NM_001042545.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26258993).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTBP4	NM_001042545.2	c.1702C>A	p.Arg568Ser	missense_variant	Exon 12 of 30	ENST00000396819.8	NP_001036010.1
LTBP4	NM_001042544.1	c.1903C>A	p.Arg635Ser	missense_variant	Exon 15 of 33		NP_001036009.1
LTBP4	NM_003573.2	c.1792C>A	p.Arg598Ser	missense_variant	Exon 15 of 33		NP_003564.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTBP4	ENST00000396819.8	c.1702C>A	p.Arg568Ser	missense_variant	Exon 12 of 30	1	NM_001042545.2	ENSP00000380031.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1441072 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 716524

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.056	T;T;.
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.15	T;T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Benign	-0.88	.;N;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.88	N;N;N
REVEL	Benign	0.28
Sift	Benign	0.20	T;T;T
Sift4G	Benign	0.64	T;T;T
Polyphen		0.49	.;P;.
Vest4		0.55
MutPred		0.35		.;Gain of glycosylation at R635 (P = 0.0522);.;
MVP		0.43
MPC		0.80
ClinPred		0.74	D
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.9
Varity_R		0.20
gMVP		0.56

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

LitVar

Other links and lift over

dbSNP: rs33937741; hg19: chr19-41116455;