rs116292261

chr6-152206120-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_182961.4(SYNE1):c.23019+48G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0161 in 1,571,386 control chromosomes in the GnomAD database, including 1,446 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.052 (582 hom., cov: 33)
  • Exomes 𝑓: 0.012 (864 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.189

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 6-152206120-C-T is Benign according to our data. Variant chr6-152206120-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 262184.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_182961.4	c.23019+48G>A		intron_variant		ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000367255.10	c.23019+48G>A		intron_variant		1	NM_182961.4	P1

Frequencies

GnomAD3 genomes AF: 0.0522 AC: 7942 AN: 152180 Hom.: 580 Cov.: 33

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0217

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.0515

Gnomad SAS AF: 0.0801

Gnomad FIN AF: 0.0147

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00181

Gnomad OTH AF: 0.0411

GnomAD3 exomes AF: 0.0269 AC: 6364 AN: 236986 Hom.: 325 AF XY: 0.0267 AC XY: 3422 AN XY: 128196

Gnomad AFR exome AF: 0.167

Gnomad AMR exome AF: 0.00888

Gnomad ASJ exome AF: 0.00214

Gnomad EAS exome AF: 0.0460

Gnomad SAS exome AF: 0.0712

Gnomad FIN exome AF: 0.0142

Gnomad NFE exome AF: 0.00173

Gnomad OTH exome AF: 0.0160

GnomAD4 exome AF: 0.0123 AC: 17396 AN: 1419088 Hom.: 864 Cov.: 28 AF XY: 0.0135 AC XY: 9552 AN XY: 707482

Gnomad4 AFR exome AF: 0.163

Gnomad4 AMR exome AF: 0.0108

Gnomad4 ASJ exome AF: 0.00194

Gnomad4 EAS exome AF: 0.0727

Gnomad4 SAS exome AF: 0.0663

Gnomad4 FIN exome AF: 0.0151

Gnomad4 NFE exome AF: 0.000923

Gnomad4 OTH exome AF: 0.0208

GnomAD4 genome AF: 0.0523 AC: 7967 AN: 152298 Hom.: 582 Cov.: 33 AF XY: 0.0540 AC XY: 4019 AN XY: 74482

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.0216

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.0518

Gnomad4 SAS AF: 0.0796

Gnomad4 FIN AF: 0.0147

Gnomad4 NFE AF: 0.00181

Gnomad4 OTH AF: 0.0407

Alfa AF: 0.0287 Hom.: 88

Bravo AF: 0.0558

Asia WGS AF: 0.0650 AC: 225 AN: 3476

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 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.29
Dann	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs116292261; hg19: chr6-152527255;