chr21-46188666-G-A

Position:

• chr21-46188666-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002340.6(LSS):​c.*2438C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 470,372 control chromosomes in the GnomAD database, including 79,362 homozygotes. 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 0.57 (24748 hom., cov: 29)
  • Exomes 𝑓: 0.58 (54614 hom.)
• Consequence: LSS NM_002340.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.686

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]

ENSG00000228404 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LSS	NM_002340.6	c.*2438C>T		3_prime_UTR_variant	22/22	ENST00000397728.8	NP_002331.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LSS	ENST00000397728	c.*2438C>T		3_prime_UTR_variant	22/22	1	NM_002340.6	ENSP00000380837.2

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86278 AN: 151502 Hom.: 24745 Cov.: 29

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.593

GnomAD3 exomes AF: 0.576 AC: 87443 AN: 151736 Hom.: 25522 AF XY: 0.583 AC XY: 47512 AN XY: 81530

Gnomad AFR exome AF: 0.524

Gnomad AMR exome AF: 0.471

Gnomad ASJ exome AF: 0.677

Gnomad EAS exome AF: 0.684

Gnomad SAS exome AF: 0.589

Gnomad FIN exome AF: 0.571

Gnomad NFE exome AF: 0.587

Gnomad OTH exome AF: 0.600

GnomAD4 exome AF: 0.583 AC: 185698 AN: 318754 Hom.: 54614 Cov.: 0 AF XY: 0.587 AC XY: 105730 AN XY: 180066

Gnomad4 AFR exome AF: 0.525

Gnomad4 AMR exome AF: 0.471

Gnomad4 ASJ exome AF: 0.679

Gnomad4 EAS exome AF: 0.693

Gnomad4 SAS exome AF: 0.593

Gnomad4 FIN exome AF: 0.567

Gnomad4 NFE exome AF: 0.587

Gnomad4 OTH exome AF: 0.604

GnomAD4 genome AF: 0.569 AC: 86311 AN: 151618 Hom.: 24748 Cov.: 29 AF XY: 0.569 AC XY: 42127 AN XY: 74096

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.528

Gnomad4 ASJ AF: 0.687

Gnomad4 EAS AF: 0.689

Gnomad4 SAS AF: 0.580

Gnomad4 FIN AF: 0.572

Gnomad4 NFE AF: 0.584

Gnomad4 OTH AF: 0.589

Alfa AF: 0.580 Hom.: 32795

Bravo AF: 0.566

Asia WGS AF: 0.595 AC: 2070 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.68

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: rs2968; hg19: chr21-47608580; COSMIC: COSV52433261; COSMIC: COSV52433261;