rs10880

Variant names:

• chr19-40622404-C-G
• NM_001042545.2:c.3221C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-40622404-C-G
• chr19-40622404-C-T

Variant summary

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

The NM_001042545.2(LTBP4):​c.3221C>G​(p.Thr1074Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000729 in 1,371,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict 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. T1074M) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: LTBP4 NM_001042545.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.152

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.3221C>G	p.Thr1074Arg	missense_variant	Exon 23 of 30	ENST00000396819.8	NP_001036010.1
LTBP4	NM_001042544.1	c.3422C>G	p.Thr1141Arg	missense_variant	Exon 26 of 33		NP_001036009.1
LTBP4	NM_003573.2	c.3311C>G	p.Thr1104Arg	missense_variant	Exon 26 of 33		NP_003564.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTBP4	ENST00000396819.8	c.3221C>G	p.Thr1074Arg	missense_variant	Exon 23 of 30	1	NM_001042545.2	ENSP00000380031.5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 7.29e-7 AC: 1 AN: 1371886 Hom.: 0 Cov.: 36 AF XY: 0.00000149 AC XY: 1 AN XY: 671214

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: 9.43e-7

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
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	16
DANN	Benign	0.81
DEOGEN2	Benign	0.078	T;T;.
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.68	T;T;T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.098	T;T;T
MetaSVM	Benign	-0.85	T
PrimateAI	Uncertain	0.64	T
REVEL	Benign	0.23
Sift4G	Benign	0.54	T;T;T
Polyphen		0.39	.;B;.
Vest4		0.30
MutPred		0.27		.;Loss of glycosylation at T1141 (P = 0.0126);.;
MVP		0.26
MPC		0.39
ClinPred		0.19	T
GERP RS		3.8
Varity_R		0.074
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.25		Position offset: 1

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: chr19-41128309;