rs746506861

Variant names:

• chr19-40601598-C-G
• NM_001042545.2:c.211C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-40601598-C-G
• chr19-40601598-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.211C>G​(p.Pro71Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000797 in 1,255,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: LTBP4 NM_001042545.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.336

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=0.25116092).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTBP4	NM_001042545.2	c.211C>G	p.Pro71Ala	missense_variant	Exon 1 of 30	ENST00000396819.8	NP_001036010.1
LTBP4	NM_001042544.1	c.451+1421C>G		intron_variant	Intron 4 of 32		NP_001036009.1
LTBP4	NM_003573.2	c.340+1421C>G		intron_variant	Intron 4 of 32		NP_003564.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTBP4	ENST00000396819.8	c.211C>G	p.Pro71Ala	missense_variant	Exon 1 of 30	1	NM_001042545.2	ENSP00000380031.5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 7.97e-7 AC: 1 AN: 1255178 Hom.: 0 Cov.: 31 AF XY: 0.00000163 AC XY: 1 AN XY: 614170

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: 0.0000167

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	23
DANN	Uncertain	0.99
Eigen	Benign	-0.036
Eigen_PC	Benign	0.00073
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.50	T
M_CAP	Pathogenic	0.76	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.65	T
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.18
Sift	Benign	0.46	T
Sift4G	Benign	0.73	T
Vest4		0.27
MutPred		0.31		Gain of catalytic residue at P71 (P = 0.0301);
MVP		0.53
ClinPred		0.41	T
GERP RS		2.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr19-41107504;