dbSNP rs117623694: SYNE1:c.15918-49G>A (chr6-152321935-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_182961.4(SYNE1):c.15918-49G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0346 in 1,608,414 control chromosomes in the GnomAD database, including 1,149 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 63 hom., cov: 32)

Exomes 𝑓: 0.036 ( 1086 hom. )

Consequence

SYNE1
NM_182961.4 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.370

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 6-152321935-C-T is Benign according to our data. Variant chr6-152321935-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 262166.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0241 (3673/152258) while in subpopulation NFE AF= 0.0399 (2715/68014). AF 95% confidence interval is 0.0387. There are 63 homozygotes in gnomad4. There are 1643 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3673 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4 link	c.15918-49G>A		intron_variant	Intron 82 of 145	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10 link	c.15918-49G>A		intron_variant	Intron 82 of 145	1	NM_182961.4	ENSP00000356224.5		Q8NF91-1

Frequencies

GnomAD3 genomes

AF:

0.0241

AC:

3673

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00714

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0212

Gnomad ASJ

AF:

0.0236

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00415

Gnomad FIN

AF:

0.0155

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0399

Gnomad OTH

AF:

0.0283

GnomAD3 exomes

AF:

0.0240

AC:

6009

AN:

250290

Hom.:

102

AF XY:

0.0243

AC XY:

3287

AN XY:

135446

show subpopulations

Gnomad AFR exome

AF:

0.00662

Gnomad AMR exome

AF:

0.0149

Gnomad ASJ exome

AF:

0.0229

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00461

Gnomad FIN exome

AF:

0.0189

Gnomad NFE exome

AF:

0.0392

Gnomad OTH exome

AF:

0.0285

GnomAD4 exome

AF:

0.0357

AC:

51960

AN:

1456156

Hom.:

1086

Cov.:

AF XY:

0.0347

AC XY:

25175

AN XY:

724644

show subpopulations

Gnomad4 AFR exome

AF:

0.00551

Gnomad4 AMR exome

AF:

0.0156

Gnomad4 ASJ exome

AF:

0.0247

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00496

Gnomad4 FIN exome

AF:

0.0187

Gnomad4 NFE exome

AF:

0.0426

Gnomad4 OTH exome

AF:

0.0291

GnomAD4 genome

AF:

0.0241

AC:

3673

AN:

152258

Hom.:

Cov.:

AF XY:

0.0221

AC XY:

1643

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00712

Gnomad4 AMR

AF:

0.0212

Gnomad4 ASJ

AF:

0.0236

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00436

Gnomad4 FIN

AF:

0.0155

Gnomad4 NFE

AF:

0.0399

Gnomad4 OTH

AF:

0.0280

Alfa

AF:

0.0329

Hom.:

Bravo

AF:

0.0241

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2018

GeneDx

Significance: Likely 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. -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.1

DANN

Benign

0.39

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over