Variant rs61739588 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000277010.9(SIGMAR1):c.552C>T(p.Phe184=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,614,190 control chromosomes in the GnomAD database, including 1,961 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.064 ( 1076 hom., cov: 32)

Exomes 𝑓: 0.0065 ( 885 hom. )

Consequence

SIGMAR1
ENST00000277010.9 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.09

Variant links:

Genes affected

SIGMAR1 (HGNC:8157): (sigma non-opioid intracellular receptor 1) This gene encodes a receptor protein that interacts with a variety of psychotomimetic drugs, including cocaine and amphetamines. The receptor is believed to play an important role in the cellular functions of various tissues associated with the endocrine, immune, and nervous systems. As indicated by its previous name, opioid receptor sigma 1 (OPRS1), the product of this gene was erroneously thought to function as an opioid receptor; it is now thought to be a non-opioid receptor. Mutations in this gene has been associated with juvenile amyotrophic lateral sclerosis 16. Alternative splicing of this gene results in transcript variants encoding distinct isoforms. [provided by RefSeq, Aug 2013]

SIGMAR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 9-34635752-G-A is Benign according to our data. Variant chr9-34635752-G-A is described in ClinVar as [Benign]. Clinvar id is 465870.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-34635752-G-A is described in Lovd as [Likely_benign]. Variant chr9-34635752-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.09 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIGMAR1	NM_005866.4 linkuse as main transcript	c.552C>T	p.Phe184=	synonymous_variant	4/4	ENST00000277010.9	NP_005857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIGMAR1	ENST00000277010.9 linkuse as main transcript	c.552C>T	p.Phe184=	synonymous_variant	4/4	1	NM_005866.4	ENSP00000277010	P1	Q99720-1

Frequencies

GnomAD3 genomes

AF:

0.0639

AC:

9721

AN:

152186

Hom.:

1073

Cov.:

show subpopulations

Gnomad AFR

AF:

0.222

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0244

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000720

Gnomad OTH

AF:

0.0439

GnomAD3 exomes

AF:

0.0171

AC:

4287

AN:

250932

Hom.:

438

AF XY:

0.0122

AC XY:

1656

AN XY:

135692

show subpopulations

Gnomad AFR exome

AF:

0.226

Gnomad AMR exome

AF:

0.0132

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000490

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000786

Gnomad OTH exome

AF:

0.00978

GnomAD4 exome

AF:

0.00654

AC:

9554

AN:

1461886

Hom.:

885

Cov.:

AF XY:

0.00560

AC XY:

4075

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.221

Gnomad4 AMR exome

AF:

0.0140

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000765

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.000423

Gnomad4 OTH exome

AF:

0.0153

GnomAD4 genome

AF:

0.0641

AC:

9756

AN:

152304

Hom.:

1076

Cov.:

AF XY:

0.0615

AC XY:

4581

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.222

Gnomad4 AMR

AF:

0.0244

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000720

Gnomad4 OTH

AF:

0.0435

Alfa

AF:

0.0346

Hom.:

272

Bravo

AF:

0.0738

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.000818

EpiControl

AF:

0.000771

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 09, 2018	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Clinical Genetics, Academic Medical Center

- -

Autosomal recessive distal spinal muscular atrophy 2;C3280587:Amyotrophic lateral sclerosis type 16

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

3.0

DANN

Benign

0.89

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

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