Genetic Variant LSS:c.-68T>C (chr21-46228813-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000356396.8(LSS):c.-68T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 97,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000010 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LSS
ENST00000356396.8 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.70

Publications

0 publications found

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:

MCM3AP-AS1 (HGNC:16417): (MCM3AP antisense RNA 1)

MCM3AP-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000356396.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LSS	NM_002340.6	MANE Select	c.-68T>C	upstream_gene	N/A	NP_002331.3
LSS	NM_001001438.3		c.-68T>C	upstream_gene	N/A	NP_001001438.1	P48449-1
LSS	NM_001145436.2		c.-68T>C	upstream_gene	N/A	NP_001138908.1	P48449-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LSS	ENST00000356396.8	TSL:1	c.-68T>C	5_prime_UTR	Exon 1 of 23	ENSP00000348762.3	P48449-1
LSS	ENST00000457828.6	TSL:1	c.-440T>C	5_prime_UTR	Exon 1 of 21	ENSP00000409191.2	P48449-2
LSS	ENST00000908051.1		c.-68T>C	5_prime_UTR	Exon 1 of 22	ENSP00000578110.1

Frequencies

GnomAD3 genomes

AF:

0.0000103

AC:

AN:

97222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000212

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1105674

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

546714

African (AFR)

AF:

0.00

AC:

AN:

23680

American (AMR)

AF:

0.00

AC:

AN:

30594

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18904

East Asian (EAS)

AF:

0.00

AC:

AN:

25760

South Asian (SAS)

AF:

0.00

AC:

AN:

64992

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28636

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3184

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

863552

Other (OTH)

AF:

0.00

AC:

AN:

46372

GnomAD4 genome

AF:

0.0000103

AC:

AN:

97222

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

46832

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24164

American (AMR)

AF:

0.00

AC:

AN:

9096

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2408

East Asian (EAS)

AF:

0.00

AC:

AN:

2910

South Asian (SAS)

AF:

0.00

AC:

AN:

2898

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6526

Middle Eastern (MID)

AF:

0.00

AC:

AN:

204

European-Non Finnish (NFE)

AF:

0.0000212

AC:

AN:

47198

Other (OTH)

AF:

0.00

AC:

AN:

1274

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.30

(source)

DANN

Benign

0.48

PhyloP100

-2.7

PromoterAI

-0.071

Neutral

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over