11-65546806-G-C

Position:

chr11-65546806-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001130144.3(LTBP3):c.2222C>G(p.Ala741Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00699 in 1,604,476 control chromosomes in the GnomAD database, including 118 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 19 hom., cov: 32)

Exomes 𝑓: 0.0066 ( 99 hom. )

Consequence

LTBP3
NM_001130144.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.331

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0049988627).

BP6

Variant 11-65546806-G-C is Benign according to our data. Variant chr11-65546806-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 532699.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LTBP3	NM_001130144.3 link	c.2222C>G	p.Ala741Gly	missense_variant	15/28	ENST00000301873.11	NP_001123616.1	Q9NS15-1Q8WYU6
LTBP3	NM_021070.4 link	c.2222C>G	p.Ala741Gly	missense_variant	15/27		NP_066548.2	Q9NS15-2Q8WYU6
LTBP3	NM_001164266.1 link	c.1871C>G	p.Ala624Gly	missense_variant	15/27		NP_001157738.1	Q9NS15B9EG76Q8WYU6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LTBP3	ENST00000301873.11 link	c.2222C>G	p.Ala741Gly	missense_variant	15/28	2	NM_001130144.3	ENSP00000301873.5		Q9NS15-1

Frequencies

GnomAD3 genomes

AF:

0.0103

AC:

1568

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0180

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0103

Gnomad ASJ

AF:

0.0375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.00661

Gnomad OTH

AF:

0.0210

GnomAD3 exomes

AF:

0.00790

AC:

1879

AN:

237826

Hom.:

AF XY:

0.00768

AC XY:

1002

AN XY:

130458

show subpopulations

Gnomad AFR exome

AF:

0.0183

Gnomad AMR exome

AF:

0.00753

Gnomad ASJ exome

AF:

0.0351

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00268

Gnomad FIN exome

AF:

0.000387

Gnomad NFE exome

AF:

0.00737

Gnomad OTH exome

AF:

0.0184

GnomAD4 exome

AF:

0.00665

AC:

9653

AN:

1452188

Hom.:

Cov.:

AF XY:

0.00678

AC XY:

4898

AN XY:

722722

show subpopulations

Gnomad4 AFR exome

AF:

0.0179

Gnomad4 AMR exome

AF:

0.00832

Gnomad4 ASJ exome

AF:

0.0351

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00284

Gnomad4 FIN exome

AF:

0.000786

Gnomad4 NFE exome

AF:

0.00565

Gnomad4 OTH exome

AF:

0.0120

GnomAD4 genome

AF:

0.0103

AC:

1563

AN:

152288

Hom.:

Cov.:

AF XY:

0.00965

AC XY:

719

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0179

Gnomad4 AMR

AF:

0.0103

Gnomad4 ASJ

AF:

0.0375

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00662

Gnomad4 OTH

AF:

0.0208

Alfa

AF:

0.00830

Hom.:

Bravo

AF:

0.0118

ESP6500AA

AF:

0.0155

AC:

ESP6500EA

AF:

0.00701

AC:

ExAC

AF:

0.00715

AC:

864

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0117

EpiControl

AF:

0.0104

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

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

- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 13, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

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

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.30

.;T;.;T;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.031

T;T;T;T;T

MetaRNN

Benign

0.0050

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.79

N;N;.;.;.

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.6

N;N;N;N;N

REVEL

Benign

0.076

Sift

Benign

0.24

T;T;T;T;T

Sift4G

Benign

0.37

T;T;T;.;T

Polyphen

0.089

B;B;B;B;.

Vest4

0.35

MVP

0.23

ClinPred

0.019

GERP RS

4.1

Varity_R

0.16

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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