Variant 11-6394652-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000543.5(SMPD1):c.*45G>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 0.142 in 1,531,524 control chromosomes in the GnomAD database, including 16,955 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2501 hom., cov: 33)

Exomes 𝑓: 0.14 ( 14454 hom. )

Consequence

SMPD1
NM_000543.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.11

Variant links:

Genes affected

SMPD1 (HGNC:11120): (sphingomyelin phosphodiesterase 1) The protein encoded by this gene is a lysosomal acid sphingomyelinase that converts sphingomyelin to ceramide. The encoded protein also has phospholipase C activity. Defects in this gene are a cause of Niemann-Pick disease type A (NPA) and Niemann-Pick disease type B (NPB). Multiple transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2010]

SMPD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 11-6394652-G-A is Benign according to our data. Variant chr11-6394652-G-A is described in ClinVar as [Benign]. Clinvar id is 305208.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMPD1	NM_000543.5 linkuse as main transcript	c.*45G>A		3_prime_UTR_variant	6/6	ENST00000342245.9	NP_000534.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMPD1	ENST00000342245.9 linkuse as main transcript	c.*45G>A		3_prime_UTR_variant	6/6	1	NM_000543.5	ENSP00000340409	P3	P17405-1

Frequencies

GnomAD3 genomes

AF:

0.166

AC:

25286

AN:

152168

Hom.:

2493

Cov.:

show subpopulations

Gnomad AFR

AF:

0.273

Gnomad AMI

AF:

0.116

Gnomad AMR

AF:

0.116

Gnomad ASJ

AF:

0.116

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.159

Gnomad FIN

AF:

0.0985

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.139

Gnomad OTH

AF:

0.163

GnomAD3 exomes

AF:

0.131

AC:

28896

AN:

220964

Hom.:

2263

AF XY:

0.133

AC XY:

16270

AN XY:

122172

show subpopulations

Gnomad AFR exome

AF:

0.283

Gnomad AMR exome

AF:

0.0798

Gnomad ASJ exome

AF:

0.129

Gnomad EAS exome

AF:

0.00402

Gnomad SAS exome

AF:

0.174

Gnomad FIN exome

AF:

0.105

Gnomad NFE exome

AF:

0.138

Gnomad OTH exome

AF:

0.145

GnomAD4 exome

AF:

0.139

AC:

191808

AN:

1379238

Hom.:

14454

Cov.:

AF XY:

0.140

AC XY:

96671

AN XY:

689874

show subpopulations

Gnomad4 AFR exome

AF:

0.278

Gnomad4 AMR exome

AF:

0.0848

Gnomad4 ASJ exome

AF:

0.129

Gnomad4 EAS exome

AF:

0.00313

Gnomad4 SAS exome

AF:

0.175

Gnomad4 FIN exome

AF:

0.107

Gnomad4 NFE exome

AF:

0.141

Gnomad4 OTH exome

AF:

0.140

GnomAD4 genome

AF:

0.166

AC:

25320

AN:

152286

Hom.:

2501

Cov.:

AF XY:

0.163

AC XY:

12174

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.273

Gnomad4 AMR

AF:

0.116

Gnomad4 ASJ

AF:

0.116

Gnomad4 EAS

AF:

0.00212

Gnomad4 SAS

AF:

0.160

Gnomad4 FIN

AF:

0.0985

Gnomad4 NFE

AF:

0.139

Gnomad4 OTH

AF:

0.161

Alfa

AF:

0.145

Hom.:

2297

Bravo

AF:

0.172

Asia WGS

AF:

0.0850

AC:

294

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Niemann-Pick disease, type A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.12

DANN

Benign

0.61

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over