6-152367432-C-T

Variant names:

• chr6-152367432-C-T
• rs7775637
• ENST00000471834.1:n.2896G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000471834.1(SYNE1):​n.2896G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.907 in 1,607,646 control chromosomes in the GnomAD database, including 663,887 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.92 (64219 hom., cov: 32)
  • Exomes 𝑓: 0.91 (599668 hom.)
• Consequence: SYNE1 ENST00000471834.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -5.96
• Publications: 7 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 6-152367432-C-T is Benign according to our data. Variant chr6-152367432-C-T is described in ClinVar as Benign. ClinVar VariationId is 262206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000471834.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE1	NM_182961.4	MANE Select	c.9808-50G>A		intron	N/A	NP_892006.3
	SYNE1	NM_033071.5		c.9829-50G>A		intron	N/A	NP_149062.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE1	ENST00000471834.1	TSL:1	n.2896G>A		non_coding_transcript_exon	Exon 5 of 19
	SYNE1	ENST00000367255.10	TSL:1 MANE Select	c.9808-50G>A		intron	N/A	ENSP00000356224.5
	SYNE1	ENST00000423061.6	TSL:1	c.9829-50G>A		intron	N/A	ENSP00000396024.1

Frequencies

GnomAD3 genomes AF: 0.917 AC: 139458 AN: 152158 Hom.: 64154 Cov.: 32

Gnomad AFR AF: 0.964

Gnomad AMI AF: 0.891

Gnomad AMR AF: 0.845

Gnomad ASJ AF: 0.852

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.936

Gnomad MID AF: 0.790

Gnomad NFE AF: 0.923

Gnomad OTH AF: 0.899

GnomAD2 exomes AF: 0.869 AC: 214568 AN: 246972 AF XY: 0.867

Gnomad AFR exome AF: 0.966

Gnomad AMR exome AF: 0.746

Gnomad ASJ exome AF: 0.861

Gnomad EAS exome AF: 0.856

Gnomad FIN exome AF: 0.935

Gnomad NFE exome AF: 0.922

Gnomad OTH exome AF: 0.881

GnomAD4 exome AF: 0.906 AC: 1318425 AN: 1455370 Hom.: 599668 Cov.: 34 AF XY: 0.901 AC XY: 652889 AN XY: 724390

African (AFR) AF: 0.963 AC: 32222 AN: 33462

American (AMR) AF: 0.761 AC: 34011 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.860 AC: 22481 AN: 26136

East Asian (EAS) AF: 0.888 AC: 35239 AN: 39680

South Asian (SAS) AF: 0.733 AC: 63197 AN: 86220

European-Finnish (FIN) AF: 0.931 AC: 44616 AN: 47906

Middle Eastern (MID) AF: 0.841 AC: 4852 AN: 5766

European-Non Finnish (NFE) AF: 0.925 AC: 1027801 AN: 1111162

Other (OTH) AF: 0.895 AC: 54006 AN: 60326

GnomAD4 genome AF: 0.917 AC: 139585 AN: 152276 Hom.: 64219 Cov.: 32 AF XY: 0.912 AC XY: 67906 AN XY: 74466

African (AFR) AF: 0.964 AC: 40041 AN: 41546

American (AMR) AF: 0.845 AC: 12921 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.852 AC: 2958 AN: 3472

East Asian (EAS) AF: 0.858 AC: 4450 AN: 5184

South Asian (SAS) AF: 0.730 AC: 3519 AN: 4818

European-Finnish (FIN) AF: 0.936 AC: 9939 AN: 10614

Middle Eastern (MID) AF: 0.791 AC: 231 AN: 292

European-Non Finnish (NFE) AF: 0.923 AC: 62810 AN: 68032

Other (OTH) AF: 0.900 AC: 1903 AN: 2114

Alfa AF: 0.918 Hom.: 44757

Bravo AF: 0.913

Asia WGS AF: 0.808 AC: 2812 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Jun 14, 2018

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.

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0010
DANN	Benign	0.55
PhyloP100		-6.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7775637; hg19: chr6-152688567;