6-152347493-C-G

Variant names:

• chr6-152347493-C-G
• rs7762904
• NM_182961.4:c.11902-258G>C

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.11902-258G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 151,786 control chromosomes in the GnomAD database, including 24,705 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.57 (24705 hom., cov: 30)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.36

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 6-152347493-C-G is Benign according to our data. Variant chr6-152347493-C-G is described in ClinVar as [Benign]. Clinvar id is 683943.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4	c.11902-258G>C		intron_variant	Intron 72 of 145	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10	c.11902-258G>C		intron_variant	Intron 72 of 145	1	NM_182961.4	ENSP00000356224.5
SYNE1	ENST00000423061.6	c.11689-258G>C		intron_variant	Intron 71 of 145	1		ENSP00000396024.1
SYNE1	ENST00000471834.1	n.5040-258G>C		intron_variant	Intron 15 of 18	1

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85766 AN: 151668 Hom.: 24692 Cov.: 30

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.649

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.585

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.565 AC: 85821 AN: 151786 Hom.: 24705 Cov.: 30 AF XY: 0.561 AC XY: 41610 AN XY: 74164

Gnomad4 AFR AF: 0.458

Gnomad4 AMR AF: 0.608

Gnomad4 ASJ AF: 0.649

Gnomad4 EAS AF: 0.656

Gnomad4 SAS AF: 0.530

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.617

Gnomad4 OTH AF: 0.587

Alfa AF: 0.455 Hom.: 1242

Bravo AF: 0.567

Asia WGS AF: 0.597 AC: 2078 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 18, 2018

GeneDx

Significance: 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.38
DANN	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7762904; hg19: chr6-152668628;