rs214997

chr6-152441454-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.4009-184T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 152,074 control chromosomes in the GnomAD database, including 22,263 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.51 (22263 hom., cov: 33)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.517

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=-0.89).
• BP6: Variant 6-152441454-A-G is Benign according to our data. Variant chr6-152441454-A-G is described in ClinVar as [Benign]. Clinvar id is 670614.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_182961.4	c.4009-184T>C		intron_variant		ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000367255.10	c.4009-184T>C		intron_variant		1	NM_182961.4	P1

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78143 AN: 151956 Hom.: 22223 Cov.: 33

Gnomad AFR AF: 0.752

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.750

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.514 AC: 78242 AN: 152074 Hom.: 22263 Cov.: 33 AF XY: 0.512 AC XY: 38068 AN XY: 74352

Gnomad4 AFR AF: 0.752

Gnomad4 AMR AF: 0.396

Gnomad4 ASJ AF: 0.412

Gnomad4 EAS AF: 0.751

Gnomad4 SAS AF: 0.541

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.510

Alfa AF: 0.459 Hom.: 2895

Bravo AF: 0.526

Asia WGS AF: 0.627 AC: 2181 AN: 3476

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	-0.89
Cadd	Benign	0.39
Dann	Benign	0.38

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs214997; hg19: chr6-152762589;