NM_002340.6:c.2068-161T>C

Variant names:

• chr21-46191396-A-G
• rs2187118
• NM_002340.6:c.2068-161T>C

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.2068-161T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 152,012 control chromosomes in the GnomAD database, including 25,115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.57 (25115 hom., cov: 32)
• Consequence: LSS NM_002340.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.43

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=-0.92).
• BP6: Variant 21-46191396-A-G is Benign according to our data. Variant chr21-46191396-A-G is described in ClinVar as [Benign]. Clinvar id is 1233283.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LSS	NM_002340.6	c.2068-161T>C		intron_variant	Intron 21 of 21	ENST00000397728.8	NP_002331.3
LSS	NM_001001438.3	c.2068-161T>C		intron_variant	Intron 21 of 22		NP_001001438.1
LSS	NM_001145436.2	c.2035-161T>C		intron_variant	Intron 21 of 21		NP_001138908.1
LSS	NM_001145437.2	c.1828-161T>C		intron_variant	Intron 20 of 20		NP_001138909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LSS	ENST00000397728.8	c.2068-161T>C		intron_variant	Intron 21 of 21	1	NM_002340.6	ENSP00000380837.2

Frequencies

GnomAD3 genomes AF: 0.573 AC: 87019 AN: 151894 Hom.: 25110 Cov.: 32

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.595

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.573 AC: 87055 AN: 152012 Hom.: 25115 Cov.: 32 AF XY: 0.572 AC XY: 42495 AN XY: 74310

Gnomad4 AFR AF: 0.541

Gnomad4 AMR AF: 0.529

Gnomad4 ASJ AF: 0.686

Gnomad4 EAS AF: 0.690

Gnomad4 SAS AF: 0.582

Gnomad4 FIN AF: 0.571

Gnomad4 NFE AF: 0.584

Gnomad4 OTH AF: 0.591

Alfa AF: 0.565 Hom.: 4378

Bravo AF: 0.570

Asia WGS AF: 0.597 AC: 2076 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.20
DANN	Benign	0.21

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: rs2187118; hg19: chr21-47611310;