rs2296254

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_182961.4(SYNE1):c.20530-14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,611,604 control chromosomes in the GnomAD database, including 40,116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3526 hom., cov: 32)

Exomes 𝑓: 0.22 ( 36590 hom. )

Consequence

SYNE1
NM_182961.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.712

Publications

10 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive ataxia, Beauce type
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine, G2P, Orphanet, PanelApp Australia
Emery-Dreifuss muscular dystrophy 4, autosomal dominant
Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: PanelApp Australia, Illumina, Ambry Genetics, Labcorp Genetics (formerly Invitae)
arthrogryposis multiplex congenita 3, myogenic type
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
autosomal dominant Emery-Dreifuss muscular dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
autosomal recessive myogenic arthrogryposis multiplex congenita
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SYNE1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_182961.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 6-152233977-C-T is Benign according to our data. Variant chr6-152233977-C-T is described in ClinVar as Benign. ClinVar VariationId is 262178.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182961.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE1	NM_182961.4	MANE Select	c.20530-14G>A		intron	N/A	NP_892006.3	Q8NF91-1
	SYNE1	NM_033071.5		c.20317-14G>A		intron	N/A	NP_149062.2	Q8NF91-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SYNE1	ENST00000367255.10	TSL:1 MANE Select	c.20530-14G>A	intron	N/A	ENSP00000356224.5	Q8NF91-1
SYNE1	ENST00000423061.6	TSL:1	c.20317-14G>A	intron	N/A	ENSP00000396024.1	A0A0C4DG40
SYNE1	ENST00000367256.9	TSL:1	n.4222-14G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.195

AC:

29647

AN:

151976

Hom.:

3519

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0747

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.361

Gnomad ASJ

AF:

0.180

Gnomad EAS

AF:

0.227

Gnomad SAS

AF:

0.226

Gnomad FIN

AF:

0.257

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.210

GnomAD2 exomes

AF:

0.243

AC:

60622

AN:

249212

AF XY:

0.236

show subpopulations

Gnomad AFR exome

AF:

0.0730

Gnomad AMR exome

AF:

0.451

Gnomad ASJ exome

AF:

0.178

Gnomad EAS exome

AF:

0.219

Gnomad FIN exome

AF:

0.262

Gnomad NFE exome

AF:

0.217

Gnomad OTH exome

AF:

0.248

GnomAD4 exome

AF:

0.217

AC:

317166

AN:

1459508

Hom.:

36590

Cov.:

AF XY:

0.217

AC XY:

157391

AN XY:

726090

show subpopulations

African (AFR)

AF:

0.0729

AC:

2438

AN:

33454

American (AMR)

AF:

0.442

AC:

19733

AN:

44638

Ashkenazi Jewish (ASJ)

AF:

0.179

AC:

4668

AN:

26114

East Asian (EAS)

AF:

0.237

AC:

9383

AN:

39652

South Asian (SAS)

AF:

0.216

AC:

18645

AN:

86180

European-Finnish (FIN)

AF:

0.263

AC:

13901

AN:

52864

Middle Eastern (MID)

AF:

0.238

AC:

1370

AN:

5756

European-Non Finnish (NFE)

AF:

0.211

AC:

234110

AN:

1110540

Other (OTH)

AF:

0.214

AC:

12918

AN:

60310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

12419

24838

37256

49675

62094

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8134

16268

24402

32536

40670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.195

AC:

29682

AN:

152096

Hom.:

3526

Cov.:

AF XY:

0.201

AC XY:

14976

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.0751

AC:

3118

AN:

41500

American (AMR)

AF:

0.361

AC:

5515

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.180

AC:

623

AN:

3470

East Asian (EAS)

AF:

0.227

AC:

1170

AN:

5162

South Asian (SAS)

AF:

0.225

AC:

1088

AN:

4826

European-Finnish (FIN)

AF:

0.257

AC:

2719

AN:

10572

Middle Eastern (MID)

AF:

0.276

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.217

AC:

14756

AN:

67972

Other (OTH)

AF:

0.215

AC:

453

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1177

2353

3530

4706

5883

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

318

636

954

1272

1590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.210

Hom.:

16002

Bravo

AF:

0.197

Asia WGS

AF:

0.243

AC:

847

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

Autosomal recessive ataxia, Beauce type (1)

Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant (1)

Emery-Dreifuss muscular dystrophy 4, autosomal dominant (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

6.9

(source)

DANN

Benign

0.68

PhyloP100

0.71

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over