Variant rs11558754 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002340.6(LSS):c.363C>T(p.Ala121Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,613,614 control chromosomes in the GnomAD database, including 20,596 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1646 hom., cov: 34)

Exomes 𝑓: 0.16 ( 18950 hom. )

Consequence

LSS
NM_002340.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -4.17

Variant links:

Genes affected

LSS (HGNC:6708): (lanosterol synthase) The protein encoded by this gene catalyzes the conversion of (S)-2,3 oxidosqualene to lanosterol. The encoded protein is a member of the terpene cyclase/mutase family and catalyzes the first step in the biosynthesis of cholesterol, steroid hormones, and vitamin D. Alternative splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Feb 2009]

LSS links:

LSS (HGNC:):

LSS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 21-46222695-G-A is Benign according to our data. Variant chr21-46222695-G-A is described in ClinVar as [Benign]. Clinvar id is 677219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.18 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LSS	NM_002340.6 linkuse as main transcript	c.363C>T	p.Ala121Ala	synonymous_variant	4/22	ENST00000397728.8	NP_002331.3
LSS	NM_001001438.3 linkuse as main transcript	c.363C>T	p.Ala121Ala	synonymous_variant	4/23		NP_001001438.1
LSS	NM_001145436.2 linkuse as main transcript	c.363C>T	p.Ala121Ala	synonymous_variant	4/22		NP_001138908.1
LSS	NM_001145437.2 linkuse as main transcript	c.123C>T	p.Ala41Ala	synonymous_variant	3/21		NP_001138909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LSS	ENST00000397728.8 linkuse as main transcript	c.363C>T	p.Ala121Ala	synonymous_variant	4/22	1	NM_002340.6	ENSP00000380837.2		P48449-1

Frequencies

GnomAD3 genomes

AF:

0.144

AC:

21859

AN:

152176

Hom.:

1644

Cov.:

show subpopulations

Gnomad AFR

AF:

0.133

Gnomad AMI

AF:

0.130

Gnomad AMR

AF:

0.137

Gnomad ASJ

AF:

0.120

Gnomad EAS

AF:

0.0987

Gnomad SAS

AF:

0.0890

Gnomad FIN

AF:

0.0881

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.169

Gnomad OTH

AF:

0.154

GnomAD3 exomes

AF:

0.136

AC:

34011

AN:

250330

Hom.:

2441

AF XY:

0.137

AC XY:

18485

AN XY:

135382

show subpopulations

Gnomad AFR exome

AF:

0.131

Gnomad AMR exome

AF:

0.122

Gnomad ASJ exome

AF:

0.121

Gnomad EAS exome

AF:

0.101

Gnomad SAS exome

AF:

0.0998

Gnomad FIN exome

AF:

0.0881

Gnomad NFE exome

AF:

0.166

Gnomad OTH exome

AF:

0.144

GnomAD4 exome

AF:

0.158

AC:

230683

AN:

1461320

Hom.:

18950

Cov.:

AF XY:

0.157

AC XY:

113788

AN XY:

726954

show subpopulations

Gnomad4 AFR exome

AF:

0.134

Gnomad4 AMR exome

AF:

0.123

Gnomad4 ASJ exome

AF:

0.124

Gnomad4 EAS exome

AF:

0.0899

Gnomad4 SAS exome

AF:

0.103

Gnomad4 FIN exome

AF:

0.0945

Gnomad4 NFE exome

AF:

0.171

Gnomad4 OTH exome

AF:

0.151

GnomAD4 genome

AF:

0.144

AC:

21875

AN:

152294

Hom.:

1646

Cov.:

AF XY:

0.138

AC XY:

10270

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.133

Gnomad4 AMR

AF:

0.137

Gnomad4 ASJ

AF:

0.120

Gnomad4 EAS

AF:

0.0985

Gnomad4 SAS

AF:

0.0892

Gnomad4 FIN

AF:

0.0881

Gnomad4 NFE

AF:

0.169

Gnomad4 OTH

AF:

0.154

Alfa

AF:

0.155

Hom.:

801

Bravo

AF:

0.149

Asia WGS

AF:

0.106

AC:

370

AN:

3478

EpiCase

AF:

0.167

EpiControl

AF:

0.173

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 24, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

LSS-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 15, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.55

DANN

Benign

0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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