rs1322512

Positions:

• chr6-152626818-C-A
• chr6-152626818-C-G

Variant summary

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

The NM_182961.4(SYNE1):​c.67+1447G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 151,998 control chromosomes in the GnomAD database, including 34,887 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 0.68 (34887 hom., cov: 32)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.253

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_182961.4	c.67+1447G>T		intron_variant		ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000367255.10	c.67+1447G>T		intron_variant		1	NM_182961.4	P1

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102813 AN: 151880 Hom.: 34894 Cov.: 32

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.657

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.658

Gnomad EAS AF: 0.657

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.680

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

GnomAD4 genome AF: 0.677 AC: 102845 AN: 151998 Hom.: 34887 Cov.: 32 AF XY: 0.669 AC XY: 49678 AN XY: 74276

Gnomad4 AFR AF: 0.678

Gnomad4 AMR AF: 0.640

Gnomad4 ASJ AF: 0.658

Gnomad4 EAS AF: 0.656

Gnomad4 SAS AF: 0.589

Gnomad4 FIN AF: 0.597

Gnomad4 NFE AF: 0.705

Gnomad4 OTH AF: 0.679

Alfa AF: 0.700 Hom.: 45126

Bravo AF: 0.683

Asia WGS AF: 0.582 AC: 2028 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.52
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1322512; hg19: chr6-152947953;