21-46191071-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002340.6(LSS):c.*33G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00611 in 1,612,978 control chromosomes in the GnomAD database, including 419 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0048 (27 hom., cov: 33)
  • Exomes 𝑓: 0.0062 (392 hom.)
• Consequence: LSS NM_002340.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.440

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 21-46191071-C-T is Benign according to our data. Variant chr21-46191071-C-T is described in ClinVar as [Benign]. Clinvar id is 1235234.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LSS	NM_002340.6	c.*33G>A		3_prime_UTR_variant	22/22	ENST00000397728.8
LSS	NM_001001438.3	c.*33G>A		3_prime_UTR_variant	22/23
LSS	NM_001145436.2	c.*33G>A		3_prime_UTR_variant	22/22
LSS	NM_001145437.2	c.*33G>A		3_prime_UTR_variant	21/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LSS	ENST00000397728.8	c.*33G>A		3_prime_UTR_variant	22/22	1	NM_002340.6	P1

Frequencies

GnomAD3 genomes AF: 0.00476 AC: 725 AN: 152158 Hom.: 27 Cov.: 33

Gnomad AFR AF: 0.000941

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00868

Gnomad SAS AF: 0.0792

Gnomad FIN AF: 0.0214

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.0130 AC: 3211 AN: 247566 Hom.: 153 AF XY: 0.0164 AC XY: 2202 AN XY: 134116

Gnomad AFR exome AF: 0.00105

Gnomad AMR exome AF: 0.000464

Gnomad ASJ exome AF: 0.000201

Gnomad EAS exome AF: 0.00648

Gnomad SAS exome AF: 0.0837

Gnomad FIN exome AF: 0.0178

Gnomad NFE exome AF: 0.000643

Gnomad OTH exome AF: 0.00756

GnomAD4 exome AF: 0.00624 AC: 9119 AN: 1460702 Hom.: 392 Cov.: 31 AF XY: 0.00848 AC XY: 6165 AN XY: 726588

Gnomad4 AFR exome AF: 0.00123

Gnomad4 AMR exome AF: 0.000358

Gnomad4 ASJ exome AF: 0.0000768

Gnomad4 EAS exome AF: 0.0116

Gnomad4 SAS exome AF: 0.0810

Gnomad4 FIN exome AF: 0.0175

Gnomad4 NFE exome AF: 0.000210

Gnomad4 OTH exome AF: 0.00718

GnomAD4 genome AF: 0.00480 AC: 731 AN: 152276 Hom.: 27 Cov.: 33 AF XY: 0.00713 AC XY: 531 AN XY: 74456

Gnomad4 AFR AF: 0.00108

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00870

Gnomad4 SAS AF: 0.0792

Gnomad4 FIN AF: 0.0214

Gnomad4 NFE AF: 0.000323

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00108 Hom.: 0

Bravo AF: 0.00127

Asia WGS AF: 0.0480 AC: 168 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

Oct 02, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	12
Dann	Benign	0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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

Other links and lift over

dbSNP: rs78413826; hg19: chr21-47610985;