Variant rs201590889 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001130144.3(LTBP3):c.804C>T(p.Pro268=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0164 in 1,573,436 control chromosomes in the GnomAD database, including 282 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 15 hom., cov: 31)

Exomes 𝑓: 0.017 ( 267 hom. )

Consequence

LTBP3
NM_001130144.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.49

Variant links:

Genes affected

LTBP3 (HGNC:6716): (latent transforming growth factor beta binding protein 3) The protein encoded by this gene forms a complex with transforming growth factor beta (TGF-beta) proteins and may be involved in their subcellular localization. Activation of this complex requires removal of the encoded binding protein. This protein also may play a structural role in the extracellular matrix. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2010]

LTBP3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 11-65553761-G-A is Benign according to our data. Variant chr11-65553761-G-A is described in ClinVar as [Benign]. Clinvar id is 464026.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-65553761-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.49 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0119 (1805/151936) while in subpopulation NFE AF= 0.0183 (1243/67906). AF 95% confidence interval is 0.0175. There are 15 homozygotes in gnomad4. There are 845 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 15 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LTBP3	NM_001130144.3 linkuse as main transcript	c.804C>T	p.Pro268=	synonymous_variant	3/28	ENST00000301873.11	NP_001123616.1
LTBP3	NM_021070.4 linkuse as main transcript	c.804C>T	p.Pro268=	synonymous_variant	3/27		NP_066548.2
LTBP3	NM_001164266.1 linkuse as main transcript	c.453C>T	p.Pro151=	synonymous_variant	3/27		NP_001157738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LTBP3	ENST00000301873.11 linkuse as main transcript	c.804C>T	p.Pro268=	synonymous_variant	3/28	2	NM_001130144.3	ENSP00000301873	P1	Q9NS15-1

Frequencies

GnomAD3 genomes

AF:

0.0119

AC:

1805

AN:

151818

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00365

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.00577

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00167

Gnomad FIN

AF:

0.0298

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0183

Gnomad OTH

AF:

0.00815

GnomAD3 exomes

AF:

0.0127

AC:

2296

AN:

180764

Hom.:

AF XY:

0.0128

AC XY:

1272

AN XY:

99652

show subpopulations

Gnomad AFR exome

AF:

0.00352

Gnomad AMR exome

AF:

0.00289

Gnomad ASJ exome

AF:

0.00583

Gnomad EAS exome

AF:

0.000740

Gnomad SAS exome

AF:

0.00134

Gnomad FIN exome

AF:

0.0381

Gnomad NFE exome

AF:

0.0220

Gnomad OTH exome

AF:

0.0119

GnomAD4 exome

AF:

0.0169

AC:

24016

AN:

1421500

Hom.:

267

Cov.:

AF XY:

0.0164

AC XY:

11580

AN XY:

704924

show subpopulations

Gnomad4 AFR exome

AF:

0.00263

Gnomad4 AMR exome

AF:

0.00282

Gnomad4 ASJ exome

AF:

0.00558

Gnomad4 EAS exome

AF:

0.000207

Gnomad4 SAS exome

AF:

0.00188

Gnomad4 FIN exome

AF:

0.0358

Gnomad4 NFE exome

AF:

0.0196

Gnomad4 OTH exome

AF:

0.0116

GnomAD4 genome

AF:

0.0119

AC:

1805

AN:

151936

Hom.:

Cov.:

AF XY:

0.0114

AC XY:

845

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.00364

Gnomad4 AMR

AF:

0.00321

Gnomad4 ASJ

AF:

0.00577

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.00167

Gnomad4 FIN

AF:

0.0298

Gnomad4 NFE

AF:

0.0183

Gnomad4 OTH

AF:

0.00806

Alfa

AF:

0.00753

Hom.:

Bravo

AF:

0.00986

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Brachyolmia-amelogenesis imperfecta syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.72

DANN

Benign

0.89

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over