chr6-152531149-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_182961.4(SYNE1):​c.130-4974T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 151,994 control chromosomes in the GnomAD database, including 9,823 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.34 ( 9823 hom., cov: 32)

Consequence

SYNE1
NM_182961.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.39

Publications

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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.01).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SYNE1NM_182961.4 linkc.130-4974T>C intron_variant Intron 4 of 145 ENST00000367255.10 NP_892006.3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SYNE1ENST00000367255.10 linkc.130-4974T>C intron_variant Intron 4 of 145 1 NM_182961.4 ENSP00000356224.5 Q8NF91-1

Frequencies

GnomAD3 genomes
AF:
0.343
AC:
52022
AN:
151876
Hom.:
9798
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.498
Gnomad AMI
AF:
0.113
Gnomad AMR
AF:
0.291
Gnomad ASJ
AF:
0.315
Gnomad EAS
AF:
0.295
Gnomad SAS
AF:
0.325
Gnomad FIN
AF:
0.234
Gnomad MID
AF:
0.383
Gnomad NFE
AF:
0.285
Gnomad OTH
AF:
0.348
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.343
AC:
52090
AN:
151994
Hom.:
9823
Cov.:
32
AF XY:
0.338
AC XY:
25113
AN XY:
74314
show subpopulations
African (AFR)
AF:
0.499
AC:
20645
AN:
41388
American (AMR)
AF:
0.291
AC:
4441
AN:
15258
Ashkenazi Jewish (ASJ)
AF:
0.315
AC:
1092
AN:
3468
East Asian (EAS)
AF:
0.295
AC:
1519
AN:
5154
South Asian (SAS)
AF:
0.324
AC:
1565
AN:
4824
European-Finnish (FIN)
AF:
0.234
AC:
2473
AN:
10588
Middle Eastern (MID)
AF:
0.357
AC:
105
AN:
294
European-Non Finnish (NFE)
AF:
0.285
AC:
19406
AN:
67994
Other (OTH)
AF:
0.351
AC:
741
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.498
Heterozygous variant carriers
0
1650
3299
4949
6598
8248
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
504
1008
1512
2016
2520
<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:
0.309
Hom.:
1256
Bravo
AF:
0.353
Asia WGS
AF:
0.329
AC:
1143
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.17
DANN
Benign
0.35
PhyloP100
-1.4
Mutation Taster
=100/0
polymorphism (auto)

Splicing

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

Publications

Other links and lift over

dbSNP: rs7745725; hg19: chr6-152852284; API