dbSNP rs6908392: SYNE1:c.11580+15C>T (chr6-152352012-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_182961.4(SYNE1):c.11580+15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 1,611,640 control chromosomes in the GnomAD database, including 291,700 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 25249 hom., cov: 32)

Exomes 𝑓: 0.60 ( 266451 hom. )

Consequence

SYNE1
NM_182961.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.117

Variant links:

Genes affected

SYNE1 (HGNC:17089): (spectrin repeat containing nuclear envelope protein 1) This gene encodes a spectrin repeat containing protein expressed in skeletal and smooth muscle, and peripheral blood lymphocytes, that localizes to the nuclear membrane. Mutations in this gene have been associated with autosomal recessive spinocerebellar ataxia 8, also referred to as autosomal recessive cerebellar ataxia type 1 or recessive ataxia of Beauce. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

SYNE1 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=-0.82).

BP6

Variant 6-152352012-G-A is Benign according to our data. Variant chr6-152352012-G-A is described in ClinVar as [Benign]. Clinvar id is 262154.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-152352012-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4 link	c.11580+15C>T		intron_variant	Intron 70 of 145	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SYNE1	ENST00000367255.10 link	c.11580+15C>T	intron_variant	Intron 70 of 145	1	NM_182961.4	ENSP00000356224.5	Q8NF91-1
SYNE1	ENST00000423061.6 link	c.11535+15C>T	intron_variant	Intron 70 of 145	1		ENSP00000396024.1	A0A0C4DG40
SYNE1	ENST00000471834.1 link	n.4718+15C>T	intron_variant	Intron 13 of 18	1

Frequencies

GnomAD3 genomes

AF:

0.575

AC:

87282

AN:

151886

Hom.:

25231

Cov.:

show subpopulations

Gnomad AFR

AF:

0.508

Gnomad AMI

AF:

0.569

Gnomad AMR

AF:

0.611

Gnomad ASJ

AF:

0.641

Gnomad EAS

AF:

0.621

Gnomad SAS

AF:

0.537

Gnomad FIN

AF:

0.534

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.609

Gnomad OTH

AF:

0.589

GnomAD3 exomes

AF:

0.584

AC:

144990

AN:

248276

Hom.:

42673

AF XY:

0.582

AC XY:

78287

AN XY:

134430

show subpopulations

Gnomad AFR exome

AF:

0.503

Gnomad AMR exome

AF:

0.602

Gnomad ASJ exome

AF:

0.647

Gnomad EAS exome

AF:

0.605

Gnomad SAS exome

AF:

0.526

Gnomad FIN exome

AF:

0.548

Gnomad NFE exome

AF:

0.604

Gnomad OTH exome

AF:

0.588

GnomAD4 exome

AF:

0.603

AC:

880097

AN:

1459634

Hom.:

266451

Cov.:

AF XY:

0.600

AC XY:

436084

AN XY:

726236

show subpopulations

Gnomad4 AFR exome

AF:

0.494

Gnomad4 AMR exome

AF:

0.604

Gnomad4 ASJ exome

AF:

0.648

Gnomad4 EAS exome

AF:

0.640

Gnomad4 SAS exome

AF:

0.525

Gnomad4 FIN exome

AF:

0.546

Gnomad4 NFE exome

AF:

0.613

Gnomad4 OTH exome

AF:

0.595

GnomAD4 genome

AF:

0.575

AC:

87345

AN:

152006

Hom.:

25249

Cov.:

AF XY:

0.571

AC XY:

42388

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.508

Gnomad4 AMR

AF:

0.612

Gnomad4 ASJ

AF:

0.641

Gnomad4 EAS

AF:

0.620

Gnomad4 SAS

AF:

0.535

Gnomad4 FIN

AF:

0.534

Gnomad4 NFE

AF:

0.609

Gnomad4 OTH

AF:

0.591

Alfa

AF:

0.606

Hom.:

48561

Bravo

AF:

0.578

Asia WGS

AF:

0.594

AC:

2067

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 25, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Autosomal recessive ataxia, Beauce type

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Emery-Dreifuss muscular dystrophy 4, autosomal dominant

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Arthrogryposis multiplex congenita 3, myogenic type

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.3

DANN

Benign

0.20

Splicing

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