rs6557210

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.19471-18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 1,470,016 control chromosomes in the GnomAD database, including 301,379 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 32283 hom., cov: 32)

Exomes 𝑓: 0.64 ( 269096 hom. )

Consequence

SYNE1
NM_182961.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 1.90

Publications

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

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=-0.9).

BP6

Variant 6-152249280-G-A is Benign according to our data. Variant chr6-152249280-G-A is described in ClinVar as Benign. ClinVar VariationId is 262176.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.86 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.19471-18C>T		intron	N/A	NP_892006.3	Q8NF91-1
	SYNE1	NM_033071.5		c.19258-18C>T		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.19471-18C>T	intron	N/A	ENSP00000356224.5	Q8NF91-1
SYNE1	ENST00000423061.6	TSL:1	c.19258-18C>T	intron	N/A	ENSP00000396024.1	A0A0C4DG40
SYNE1	ENST00000367256.9	TSL:1	n.3163-18C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.647

AC:

98262

AN:

151940

Hom.:

32247

Cov.:

show subpopulations

Gnomad AFR

AF:

0.652

Gnomad AMI

AF:

0.618

Gnomad AMR

AF:

0.610

Gnomad ASJ

AF:

0.617

Gnomad EAS

AF:

0.882

Gnomad SAS

AF:

0.664

Gnomad FIN

AF:

0.786

Gnomad MID

AF:

0.490

Gnomad NFE

AF:

0.615

Gnomad OTH

AF:

0.596

GnomAD2 exomes

AF:

0.658

AC:

165266

AN:

250984

AF XY:

0.655

show subpopulations

Gnomad AFR exome

AF:

0.655

Gnomad AMR exome

AF:

0.621

Gnomad ASJ exome

AF:

0.610

Gnomad EAS exome

AF:

0.895

Gnomad FIN exome

AF:

0.780

Gnomad NFE exome

AF:

0.613

Gnomad OTH exome

AF:

0.642

GnomAD4 exome

AF:

0.637

AC:

839004

AN:

1317958

Hom.:

269096

Cov.:

AF XY:

0.635

AC XY:

421899

AN XY:

664054

show subpopulations

African (AFR)

AF:

0.654

AC:

19981

AN:

30570

American (AMR)

AF:

0.623

AC:

27763

AN:

44562

Ashkenazi Jewish (ASJ)

AF:

0.607

AC:

15319

AN:

25226

East Asian (EAS)

AF:

0.878

AC:

34355

AN:

39114

South Asian (SAS)

AF:

0.661

AC:

55059

AN:

83280

European-Finnish (FIN)

AF:

0.782

AC:

41650

AN:

53270

Middle Eastern (MID)

AF:

0.497

AC:

2709

AN:

5456

European-Non Finnish (NFE)

AF:

0.618

AC:

606364

AN:

980778

Other (OTH)

AF:

0.643

AC:

35804

AN:

55702

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

14385

28770

43156

57541

71926

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15652

31304

46956

62608

78260

<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:

0.647

AC:

98349

AN:

152058

Hom.:

32283

Cov.:

AF XY:

0.654

AC XY:

48651

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.652

AC:

27005

AN:

41450

American (AMR)

AF:

0.611

AC:

9332

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.617

AC:

2141

AN:

3470

East Asian (EAS)

AF:

0.882

AC:

4571

AN:

5184

South Asian (SAS)

AF:

0.664

AC:

3200

AN:

4822

European-Finnish (FIN)

AF:

0.786

AC:

8322

AN:

10584

Middle Eastern (MID)

AF:

0.500

AC:

146

AN:

292

European-Non Finnish (NFE)

AF:

0.615

AC:

41799

AN:

67954

Other (OTH)

AF:

0.601

AC:

1272

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1751

3502

5252

7003

8754

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

796

1592

2388

3184

3980

<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:

0.614

Hom.:

46138

Bravo

AF:

0.635

Asia WGS

AF:

0.769

AC:

2673

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

Arthrogryposis multiplex congenita 3, myogenic type (1)

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

-0.90

CADD

Benign

6.0

(source)

DANN

Benign

0.57

PhyloP100

1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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