21-46191025-TG-T

Position:

• chr21-46191025-TG-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002340.6(LSS):​c.*78del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0191 in 1,555,320 control chromosomes in the GnomAD database, including 1,204 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.048 (430 hom., cov: 32)
  • Exomes 𝑓: 0.016 (774 hom.)
• Consequence: LSS NM_002340.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.116

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 21-46191025-TG-T is Benign according to our data. Variant chr21-46191025-TG-T is described in ClinVar as [Benign]. Clinvar id is 1291872.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LSS	NM_002340.6	c.*78del		3_prime_UTR_variant	22/22	ENST00000397728.8	NP_002331.3
LSS	NM_001145436.2	c.*78del		3_prime_UTR_variant	22/22		NP_001138908.1
LSS	NM_001145437.2	c.*78del		3_prime_UTR_variant	21/21		NP_001138909.1
LSS	NM_001001438.3	c.*38+40del		intron_variant			NP_001001438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LSS	ENST00000397728.8	c.*78del		3_prime_UTR_variant	22/22	1	NM_002340.6	ENSP00000380837	P1

Frequencies

GnomAD3 genomes AF: 0.0476 AC: 7232 AN: 152048 Hom.: 420 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0259

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.00541

Gnomad SAS AF: 0.0867

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.00870

Gnomad OTH AF: 0.0474

GnomAD4 exome AF: 0.0160 AC: 22433 AN: 1403156 Hom.: 774 Cov.: 25 AF XY: 0.0173 AC XY: 12047 AN XY: 697346

Gnomad4 AFR exome AF: 0.143

Gnomad4 AMR exome AF: 0.0161

Gnomad4 ASJ exome AF: 0.0116

Gnomad4 EAS exome AF: 0.00204

Gnomad4 SAS exome AF: 0.0729

Gnomad4 FIN exome AF: 0.00172

Gnomad4 NFE exome AF: 0.00853

Gnomad4 OTH exome AF: 0.0248

GnomAD4 genome AF: 0.0478 AC: 7268 AN: 152164 Hom.: 430 Cov.: 32 AF XY: 0.0470 AC XY: 3496 AN XY: 74404

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.0259

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.00542

Gnomad4 SAS AF: 0.0863

Gnomad4 FIN AF: 0.00151

Gnomad4 NFE AF: 0.00871

Gnomad4 OTH AF: 0.0536

Alfa AF: 0.0302 Hom.: 28

Bravo AF: 0.0533

Asia WGS AF: 0.0860 AC: 300 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 04, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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

Other links and lift over

dbSNP: rs142247529; hg19: chr21-47610939;