rs214989

Positions:

• chr6-152417210-A-G

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.5422-195T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,192 control chromosomes in the GnomAD database, including 2,575 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.18 (2575 hom., cov: 33)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.51

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=-0.82).
• BP6: Variant 6-152417210-A-G is Benign according to our data. Variant chr6-152417210-A-G is described in ClinVar as [Benign]. Clinvar id is 670642.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_182961.4	c.5422-195T>C		intron_variant		ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000367255.10	c.5422-195T>C		intron_variant		1	NM_182961.4	P1
SYNE1	ENST00000423061.6	c.5443-195T>C		intron_variant		1
SYNE1	ENST00000461872.6	n.5640-195T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27477 AN: 152074 Hom.: 2575 Cov.: 33

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.181 AC: 27482 AN: 152192 Hom.: 2575 Cov.: 33 AF XY: 0.180 AC XY: 13401 AN XY: 74412

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.204

Alfa AF: 0.197 Hom.: 4115

Bravo AF: 0.178

Asia WGS AF: 0.242 AC: 841 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	-0.82
CADD	Benign	5.4
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs214989; hg19: chr6-152738345;