Variant 21-46228755-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_002340.6(LSS):c.-10T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00037 in 1,588,256 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00038 ( 4 hom. )

Consequence

LSS
NM_002340.6 5_prime_UTR

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.23

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 -13 ACMG points.

BP4

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

BP6

Variant 21-46228755-A-T is Benign according to our data. Variant chr21-46228755-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 3054304.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000271 (40/147764) while in subpopulation SAS AF= 0.00364 (17/4674). AF 95% confidence interval is 0.00232. There are 0 homozygotes in gnomad4. There are 26 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
LSS	NM_002340.6 linkuse as main transcript	c.-10T>A	5_prime_UTR_variant	1/22	ENST00000397728.8	NP_002331.3
LSS	NM_001001438.3 linkuse as main transcript	c.-10T>A	5_prime_UTR_variant	1/23		NP_001001438.1
LSS	NM_001145436.2 linkuse as main transcript	c.-10T>A	5_prime_UTR_variant	1/22		NP_001138908.1
LSS	NM_001145437.2 linkuse as main transcript	c.-382T>A	5_prime_UTR_variant	1/21		NP_001138909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LSS	ENST00000397728.8 linkuse as main transcript	c.-10T>A		5_prime_UTR_variant	1/22	1	NM_002340.6	ENSP00000380837.2		P48449-1

Frequencies

GnomAD3 genomes

AF:

0.000271

AC:

AN:

147646

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000250

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000271

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00363

Gnomad FIN

AF:

0.0000974

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000240

Gnomad OTH

AF:

0.000500

GnomAD3 exomes

AF:

0.000727

AC:

157

AN:

215834

Hom.:

AF XY:

0.000919

AC XY:

110

AN XY:

119636

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000602

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00450

Gnomad FIN exome

AF:

0.0000851

Gnomad NFE exome

AF:

0.000196

Gnomad OTH exome

AF:

0.000736

GnomAD4 exome

AF:

0.000380

AC:

547

AN:

1440492

Hom.:

Cov.:

AF XY:

0.000512

AC XY:

367

AN XY:

716784

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000680

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000258

Gnomad4 SAS exome

AF:

0.00401

Gnomad4 FIN exome

AF:

0.000147

Gnomad4 NFE exome

AF:

0.000143

Gnomad4 OTH exome

AF:

0.000469

GnomAD4 genome

AF:

0.000271

AC:

AN:

147764

Hom.:

Cov.:

AF XY:

0.000360

AC XY:

AN XY:

72138

show subpopulations

Gnomad4 AFR

AF:

0.0000250

Gnomad4 AMR

AF:

0.000271

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00364

Gnomad4 FIN

AF:

0.0000974

Gnomad4 NFE

AF:

0.000240

Gnomad4 OTH

AF:

0.000495

Alfa

AF:

0.000299

Hom.:

Bravo

AF:

0.000212

Asia WGS

AF:

0.00202

AC:

AN:

3472

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

LSS-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 09, 2022

This variant is classified as likely 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

5.4

DANN

Benign

0.50

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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