rs71659863

chr6-152430083-ATAG-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_182961.4(SYNE1):c.4788+26_4788+28del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,451,990 control chromosomes in the GnomAD database, including 16,016 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1833 hom., cov: 29)
  • Exomes 𝑓: 0.14 (14183 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.30

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 6-152430083-ATAG-A is Benign according to our data. Variant chr6-152430083-ATAG-A is described in ClinVar as [Likely_benign]. Clinvar id is 262197.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_182961.4	c.4788+26_4788+28del		intron_variant		ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000367255.10	c.4788+26_4788+28del		intron_variant		1	NM_182961.4	P1
SYNE1	ENST00000423061.6	c.4809+26_4809+28del		intron_variant		1
SYNE1	ENST00000461872.6	n.5006+26_5006+28del		intron_variant, non_coding_transcript_variant		1
SYNE1	ENST00000367253.8	c.4788+26_4788+28del		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22667 AN: 151972 Hom.: 1831 Cov.: 29

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.144

GnomAD3 exomes AF: 0.151 AC: 30065 AN: 198550 Hom.: 2784 AF XY: 0.153 AC XY: 16287 AN XY: 106384

Gnomad AFR exome AF: 0.164

Gnomad AMR exome AF: 0.0792

Gnomad ASJ exome AF: 0.124

Gnomad EAS exome AF: 0.379

Gnomad SAS exome AF: 0.165

Gnomad FIN exome AF: 0.169

Gnomad NFE exome AF: 0.129

Gnomad OTH exome AF: 0.129

GnomAD4 exome AF: 0.140 AC: 181889 AN: 1299902 Hom.: 14183 AF XY: 0.140 AC XY: 91285 AN XY: 650490

Gnomad4 AFR exome AF: 0.165

Gnomad4 AMR exome AF: 0.0863

Gnomad4 ASJ exome AF: 0.121

Gnomad4 EAS exome AF: 0.383

Gnomad4 SAS exome AF: 0.165

Gnomad4 FIN exome AF: 0.165

Gnomad4 NFE exome AF: 0.129

Gnomad4 OTH exome AF: 0.146

GnomAD4 genome AF: 0.149 AC: 22678 AN: 152088 Hom.: 1833 Cov.: 29 AF XY: 0.152 AC XY: 11298 AN XY: 74334

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.177

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.142

Alfa AF: 0.133 Hom.: 274

Bravo AF: 0.147

Asia WGS AF: 0.242 AC: 838 AN: 3454

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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 v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs71659863; hg19: chr6-152751218;