rs214959

chr6-152381686-G-Achr6-152381686-G-Cchr6-152381686-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_182961.4(SYNE1):c.8653-324C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 378,674 control chromosomes in the GnomAD database, including 70,372 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.64 (33355 hom., cov: 31)
  • Exomes 𝑓: 0.56 (37017 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.740

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-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 6-152381686-G-A is Benign according to our data. Variant chr6-152381686-G-A is described in ClinVar as [Benign]. Clinvar id is 683934.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_182961.4	c.8653-324C>T		intron_variant		ENST00000367255.10
SYNE1-AS1	NR_120501.1	n.691G>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000367255.10	c.8653-324C>T		intron_variant		1	NM_182961.4	P1
SYNE1	ENST00000423061.6	c.8674-324C>T		intron_variant		1
SYNE1	ENST00000454018.7	c.4-324C>T		intron_variant		1
SYNE1	ENST00000461872.6	n.8871-324C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97493 AN: 151878 Hom.: 33301 Cov.: 31

Gnomad AFR AF: 0.895

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.608

GnomAD4 exome AF: 0.564 AC: 127850 AN: 226678 Hom.: 37017 AF XY: 0.569 AC XY: 68907 AN XY: 121004

Gnomad4 AFR exome AF: 0.900

Gnomad4 AMR exome AF: 0.519

Gnomad4 ASJ exome AF: 0.510

Gnomad4 EAS exome AF: 0.653

Gnomad4 SAS exome AF: 0.620

Gnomad4 FIN exome AF: 0.619

Gnomad4 NFE exome AF: 0.525

Gnomad4 OTH exome AF: 0.571

GnomAD4 genome AF: 0.642 AC: 97596 AN: 151996 Hom.: 33355 Cov.: 31 AF XY: 0.644 AC XY: 47804 AN XY: 74276

Gnomad4 AFR AF: 0.895

Gnomad4 AMR AF: 0.526

Gnomad4 ASJ AF: 0.513

Gnomad4 EAS AF: 0.646

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.637

Gnomad4 NFE AF: 0.526

Gnomad4 OTH AF: 0.610

Alfa AF: 0.548 Hom.: 34868

Bravo AF: 0.645

Asia WGS AF: 0.624 AC: 2169 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	4.4
Dann	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs214959; hg19: chr6-152702821;