Variant 13-75727054-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000377534.8(LMO7):c.166G>A(p.Val56Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000157 in 1,588,018 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 3 hom. )

Consequence

LMO7
ENST00000377534.8 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.252

Variant links:

Genes affected

LMO7 (HGNC:6646): (LIM domain 7) This gene encodes a protein containing a calponin homology (CH) domain, a PDZ domain, and a LIM domain, and may be involved in protein-protein interactions. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene, however, the full-length nature of some variants is not known. [provided by RefSeq, Jan 2009]

LMO7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0068373084).

BP6

Variant 13-75727054-G-A is Benign according to our data. Variant chr13-75727054-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2210808.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMO7	NM_001306080.2 linkuse as main transcript	c.166G>A	p.Val56Ile	missense_variant	3/31	ENST00000377534.8	NP_001293009.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMO7	ENST00000377534.8 linkuse as main transcript	c.166G>A	p.Val56Ile	missense_variant	3/31	1	NM_001306080.2	ENSP00000366757	P2

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000883

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000237

AC:

AN:

249440

Hom.:

AF XY:

0.000282

AC XY:

AN XY:

134868

show subpopulations

Gnomad AFR exome

AF:

0.000311

Gnomad AMR exome

AF:

0.0000586

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000330

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000230

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000155

AC:

223

AN:

1435842

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

116

AN XY:

715850

show subpopulations

Gnomad4 AFR exome

AF:

0.000334

Gnomad4 AMR exome

AF:

0.0000899

Gnomad4 ASJ exome

AF:

0.00123

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000421

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000106

Gnomad4 OTH exome

AF:

0.000336

GnomAD4 genome

AF:

0.000171

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000883

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000236

Hom.:

Bravo

AF:

0.000276

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000255

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000219

EpiControl

AF:

0.000179

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 27, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.47

CADD

Benign

0.12

DANN

Benign

0.62

DEOGEN2

Benign

0.25

T;.;.;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.73

T;T;T;T

M_CAP

Benign

0.0081

MetaRNN

Benign

0.0068

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-1.4

.;N;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

0.32

.;N;N;.

REVEL

Benign

0.12

Sift

Benign

1.0

.;T;T;.

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.010

.;B;.;.

Vest4

0.23

MVP

0.18

ClinPred

0.0067

GERP RS

-8.0

gMVP

0.22

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