dbSNP rs9383976: SYNE1:c.21656+13T>C (chr6-152221413-A-G) – 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.21656+13T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,612,502 control chromosomes in the GnomAD database, including 52,582 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6067 hom., cov: 32)

Exomes 𝑓: 0.24 ( 46515 hom. )

Consequence

SYNE1
NM_182961.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.194

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=-0.83).

BP6

Variant 6-152221413-A-G is Benign according to our data. Variant chr6-152221413-A-G is described in ClinVar as [Benign]. Clinvar id is 262182.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-152221413-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4 link	c.21656+13T>C		intron_variant	Intron 118 of 145	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10 link	c.21656+13T>C		intron_variant	Intron 118 of 145	1	NM_182961.4	ENSP00000356224.5		Q8NF91-1

Frequencies

GnomAD3 genomes

AF:

0.272

AC:

41305

AN:

151962

Hom.:

6056

Cov.:

show subpopulations

Gnomad AFR

AF:

0.326

Gnomad AMI

AF:

0.220

Gnomad AMR

AF:

0.214

Gnomad ASJ

AF:

0.275

Gnomad EAS

AF:

0.549

Gnomad SAS

AF:

0.348

Gnomad FIN

AF:

0.353

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.215

Gnomad OTH

AF:

0.225

GnomAD3 exomes

AF:

0.282

AC:

70872

AN:

251040

Hom.:

11352

AF XY:

0.280

AC XY:

37959

AN XY:

135678

show subpopulations

Gnomad AFR exome

AF:

0.330

Gnomad AMR exome

AF:

0.268

Gnomad ASJ exome

AF:

0.277

Gnomad EAS exome

AF:

0.572

Gnomad SAS exome

AF:

0.319

Gnomad FIN exome

AF:

0.347

Gnomad NFE exome

AF:

0.213

Gnomad OTH exome

AF:

0.240

GnomAD4 exome

AF:

0.243

AC:

354551

AN:

1460422

Hom.:

46515

Cov.:

AF XY:

0.243

AC XY:

176727

AN XY:

726546

show subpopulations

Gnomad4 AFR exome

AF:

0.326

Gnomad4 AMR exome

AF:

0.260

Gnomad4 ASJ exome

AF:

0.268

Gnomad4 EAS exome

AF:

0.527

Gnomad4 SAS exome

AF:

0.317

Gnomad4 FIN exome

AF:

0.342

Gnomad4 NFE exome

AF:

0.218

Gnomad4 OTH exome

AF:

0.256

GnomAD4 genome

AF:

0.272

AC:

41362

AN:

152080

Hom.:

6067

Cov.:

AF XY:

0.279

AC XY:

20710

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.326

Gnomad4 AMR

AF:

0.215

Gnomad4 ASJ

AF:

0.275

Gnomad4 EAS

AF:

0.549

Gnomad4 SAS

AF:

0.347

Gnomad4 FIN

AF:

0.353

Gnomad4 NFE

AF:

0.215

Gnomad4 OTH

AF:

0.224

Alfa

AF:

0.222

Hom.:

8103

Bravo

AF:

0.266

Asia WGS

AF:

0.420

AC:

1457

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Clinical Genetics, Academic Medical Center

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

- -

Jan 28, 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. -

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

Significance: Benign

Review Status: no assertion criteria provided

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

- -

Autosomal recessive ataxia, Beauce type

Benign:1

Jan 12, 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. -

Emery-Dreifuss muscular dystrophy 4, autosomal dominant

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

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

-0.83

CADD

Benign

3.8

DANN

Benign

0.49

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