rs17082664

Positions:

• chr6-152417619-A-G
• chr6-152417619-A-T

Variant summary

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

The NM_182961.4(SYNE1):​c.5422-604T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,190 control chromosomes in the GnomAD database, including 2,686 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 0.17 (2686 hom., cov: 33)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_182961.4	c.5422-604T>C		intron_variant		ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000367255.10	c.5422-604T>C		intron_variant		1	NM_182961.4	P1
SYNE1	ENST00000423061.6	c.5443-604T>C		intron_variant		1
SYNE1	ENST00000461872.6	n.5640-604T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26547 AN: 152072 Hom.: 2683 Cov.: 33

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.175 AC: 26571 AN: 152190 Hom.: 2686 Cov.: 33 AF XY: 0.176 AC XY: 13120 AN XY: 74400

Gnomad4 AFR AF: 0.254

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.366

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.157

Alfa AF: 0.0741 Hom.: 103

Bravo AF: 0.175

Asia WGS AF: 0.249 AC: 863 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.0
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17082664; hg19: chr6-152738754;