rs9371581

chr6-152308451-G-Achr6-152308451-G-C

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.17346+38C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 1,612,054 control chromosomes in the GnomAD database, including 220,229 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (18551 hom., cov: 31)
  • Exomes 𝑓: 0.52 (201678 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.48

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=-0.78).
• BP6: Variant 6-152308451-G-A is Benign according to our data. Variant chr6-152308451-G-A is described in ClinVar as [Benign]. Clinvar id is 262172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_182961.4	c.17346+38C>T		intron_variant		ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000367255.10	c.17346+38C>T		intron_variant		1	NM_182961.4	P1
SYNE1	ENST00000423061.6	c.17133+38C>T		intron_variant		1
SYNE1	ENST00000367256.9	n.1038+38C>T		intron_variant, non_coding_transcript_variant		1
SYNE1	ENST00000409694.6	n.930+38C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73241 AN: 151830 Hom.: 18550 Cov.: 31

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.455

GnomAD3 exomes AF: 0.505 AC: 126889 AN: 251272 Hom.: 33336 AF XY: 0.502 AC XY: 68177 AN XY: 135812

Gnomad AFR exome AF: 0.339

Gnomad AMR exome AF: 0.425

Gnomad ASJ exome AF: 0.464

Gnomad EAS exome AF: 0.641

Gnomad SAS exome AF: 0.383

Gnomad FIN exome AF: 0.689

Gnomad NFE exome AF: 0.533

Gnomad OTH exome AF: 0.501

GnomAD4 exome AF: 0.521 AC: 761057 AN: 1460106 Hom.: 201678 Cov.: 39 AF XY: 0.518 AC XY: 376310 AN XY: 726428

Gnomad4 AFR exome AF: 0.328

Gnomad4 AMR exome AF: 0.421

Gnomad4 ASJ exome AF: 0.464

Gnomad4 EAS exome AF: 0.635

Gnomad4 SAS exome AF: 0.384

Gnomad4 FIN exome AF: 0.679

Gnomad4 NFE exome AF: 0.533

Gnomad4 OTH exome AF: 0.506

GnomAD4 genome AF: 0.482 AC: 73275 AN: 151948 Hom.: 18551 Cov.: 31 AF XY: 0.488 AC XY: 36215 AN XY: 74250

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.437

Gnomad4 ASJ AF: 0.464

Gnomad4 EAS AF: 0.647

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.696

Gnomad4 NFE AF: 0.538

Gnomad4 OTH AF: 0.454

Alfa AF: 0.514 Hom.: 42669

Bravo AF: 0.459

Asia WGS AF: 0.501 AC: 1745 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

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. -

Arthrogryposis multiplex congenita 3, myogenic type Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Autosomal recessive ataxia, Beauce type Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Emery-Dreifuss muscular dystrophy 4, autosomal dominant Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	1.5
Dann	Benign	0.84

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9371581; hg19: chr6-152629586;