rs1554783

Positions:

• chr6-152555942-A-G
• chr6-152555942-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000367255.10(SYNE1):​c.68-15921T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,144 control chromosomes in the GnomAD database, including 5,106 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (5106 hom., cov: 32)
• Consequence: SYNE1 ENST00000367255.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.244

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNE1	NM_182961.4	c.68-15921T>C		intron_variant		ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10	c.68-15921T>C		intron_variant		1	NM_182961.4	ENSP00000356224	P1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39222 AN: 152026 Hom.: 5095 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.258 AC: 39275 AN: 152144 Hom.: 5106 Cov.: 32 AF XY: 0.261 AC XY: 19438 AN XY: 74388

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.268

Alfa AF: 0.247 Hom.: 7927

Bravo AF: 0.255

Asia WGS AF: 0.253 AC: 881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.4
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1554783; hg19: chr6-152877077;