dbSNP rs9478310: SYNE1:c.18208-24A>G (chr6-152282004-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_182961.4(SYNE1):c.18208-24A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0663 in 1,610,520 control chromosomes in the GnomAD database, including 3,995 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.069 ( 421 hom., cov: 32)

Exomes 𝑓: 0.066 ( 3574 hom. )

Consequence

SYNE1
NM_182961.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.50

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 6-152282004-T-C is Benign according to our data. Variant chr6-152282004-T-C is described in ClinVar as [Benign]. Clinvar id is 262174.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-152282004-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4 link	c.18208-24A>G		intron_variant	Intron 96 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.18208-24A>G		intron_variant	Intron 96 of 145	1	NM_182961.4	ENSP00000356224.5		Q8NF91-1

Frequencies

GnomAD3 genomes

AF:

0.0691

AC:

10519

AN:

152128

Hom.:

421

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0873

Gnomad AMI

AF:

0.0980

Gnomad AMR

AF:

0.0514

Gnomad ASJ

AF:

0.124

Gnomad EAS

AF:

0.0550

Gnomad SAS

AF:

0.103

Gnomad FIN

AF:

0.0296

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0633

Gnomad OTH

AF:

0.0774

GnomAD3 exomes

AF:

0.0671

AC:

16449

AN:

245092

Hom.:

692

AF XY:

0.0707

AC XY:

9392

AN XY:

132916

show subpopulations

Gnomad AFR exome

AF:

0.0879

Gnomad AMR exome

AF:

0.0362

Gnomad ASJ exome

AF:

0.114

Gnomad EAS exome

AF:

0.0602

Gnomad SAS exome

AF:

0.116

Gnomad FIN exome

AF:

0.0282

Gnomad NFE exome

AF:

0.0639

Gnomad OTH exome

AF:

0.0763

GnomAD4 exome

AF:

0.0660

AC:

96315

AN:

1458274

Hom.:

3574

Cov.:

AF XY:

0.0683

AC XY:

49578

AN XY:

725612

show subpopulations

Gnomad4 AFR exome

AF:

0.0868

Gnomad4 AMR exome

AF:

0.0384

Gnomad4 ASJ exome

AF:

0.115

Gnomad4 EAS exome

AF:

0.0479

Gnomad4 SAS exome

AF:

0.119

Gnomad4 FIN exome

AF:

0.0313

Gnomad4 NFE exome

AF:

0.0626

Gnomad4 OTH exome

AF:

0.0778

GnomAD4 genome

AF:

0.0692

AC:

10530

AN:

152246

Hom.:

421

Cov.:

AF XY:

0.0686

AC XY:

5109

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0872

Gnomad4 AMR

AF:

0.0513

Gnomad4 ASJ

AF:

0.124

Gnomad4 EAS

AF:

0.0553

Gnomad4 SAS

AF:

0.104

Gnomad4 FIN

AF:

0.0296

Gnomad4 NFE

AF:

0.0633

Gnomad4 OTH

AF:

0.0785

Alfa

AF:

0.0757

Hom.:

148

Bravo

AF:

0.0720

Asia WGS

AF:

0.0980

AC:

341

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Jun 28, 2018

GeneDx

Significance: 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

-0.90

CADD

Benign

1.1

DANN

Benign

0.41

La Branchor

0.53

BranchPoint Hunter

1.0

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