ENST00000457828.6:c.-239C>G

Variant names:

• chr21-46228612-G-C
• rs992178133
• ENST00000457828.6:c.-239C>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The ENST00000457828.6(LSS):​c.-239C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000139 in 1,439,498 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: LSS ENST00000457828.6 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0590
• Publications: 0 publications found

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]

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

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 21-46228612-G-C is Benign according to our data. Variant chr21-46228612-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1645592.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000457828.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSS	NM_002340.6	MANE Select	c.15-13C>G		intron	N/A	NP_002331.3
	LSS	NM_001145437.2		c.-239C>G		5_prime_UTR	Exon 1 of 21	NP_001138909.1	P48449-2
	LSS	NM_001001438.3		c.15-13C>G		intron	N/A	NP_001001438.1	P48449-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSS	ENST00000457828.6	TSL:1	c.-239C>G		5_prime_UTR	Exon 1 of 21	ENSP00000409191.2	P48449-2
	LSS	ENST00000397728.8	TSL:1 MANE Select	c.15-13C>G		intron	N/A	ENSP00000380837.2	P48449-1
	LSS	ENST00000356396.8	TSL:1	c.15-13C>G		intron	N/A	ENSP00000348762.3	P48449-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000967 AC: 2 AN: 206734 AF XY: 0.00000865

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000220

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000139 AC: 20 AN: 1439498 Hom.: 0 Cov.: 33 AF XY: 0.0000126 AC XY: 9 AN XY: 716184

African (AFR) AF: 0.00 AC: 0 AN: 33136

American (AMR) AF: 0.00 AC: 0 AN: 43938

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25860

East Asian (EAS) AF: 0.00 AC: 0 AN: 39080

South Asian (SAS) AF: 0.00 AC: 0 AN: 85184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38946

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00000993 AC: 11 AN: 1107808

Other (OTH) AF: 0.000151 AC: 9 AN: 59792

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.2
DANN	Benign	0.84
PhyloP100		-0.059
PromoterAI		0.041	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs992178133; hg19: chr21-47648526;