21-46194255-T-C

Position:

• chr21-46194255-T-C

Variant summary

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

The ENST00000397728.8(LSS):​c.1988+236A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0405 in 152,226 control chromosomes in the GnomAD database, including 175 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.041 (175 hom., cov: 34)
• Consequence: LSS ENST00000397728.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.742

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=-0.88).
• BP6: Variant 21-46194255-T-C is Benign according to our data. Variant chr21-46194255-T-C is described in ClinVar as [Benign]. Clinvar id is 1183357.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LSS	NM_002340.6	c.1988+236A>G		intron_variant		ENST00000397728.8	NP_002331.3
LSS	NM_001001438.3	c.1988+236A>G		intron_variant			NP_001001438.1
LSS	NM_001145436.2	c.1955+236A>G		intron_variant			NP_001138908.1
LSS	NM_001145437.2	c.1748+236A>G		intron_variant			NP_001138909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LSS	ENST00000397728.8	c.1988+236A>G		intron_variant		1	NM_002340.6	ENSP00000380837.2

Frequencies

GnomAD3 genomes AF: 0.0406 AC: 6170 AN: 152108 Hom.: 176 Cov.: 34

Gnomad AFR AF: 0.0114

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0287

Gnomad ASJ AF: 0.0397

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00911

Gnomad FIN AF: 0.0654

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0628

Gnomad OTH AF: 0.0388

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

GnomAD4 genome AF: 0.0405 AC: 6168 AN: 152226 Hom.: 175 Cov.: 34 AF XY: 0.0393 AC XY: 2927 AN XY: 74416

Gnomad4 AFR AF: 0.0114

Gnomad4 AMR AF: 0.0286

Gnomad4 ASJ AF: 0.0397

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.00932

Gnomad4 FIN AF: 0.0654

Gnomad4 NFE AF: 0.0628

Gnomad4 OTH AF: 0.0384

Alfa AF: 0.0583 Hom.: 42

Bravo AF: 0.0366

Asia WGS AF: 0.00924 AC: 32 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

Jun 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.1
DANN	Benign	0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs79223895; hg19: chr21-47614169;