6-152149001-T-C

Position:

• chr6-152149001-T-C

Variant summary

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

The NM_182961.4(SYNE1):​c.24642+476A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 151,868 control chromosomes in the GnomAD database, including 26,595 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 0.59 (26595 hom., cov: 31)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.71

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNE1	NM_001347702.2	c.1107+476A>G		intron_variant		ENST00000354674.5	NP_001334631.1
SYNE1	NM_182961.4	c.24642+476A>G		intron_variant		ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000354674.5	c.1107+476A>G		intron_variant		5	NM_001347702.2	ENSP00000346701
SYNE1	ENST00000367255.10	c.24642+476A>G		intron_variant		1	NM_182961.4	ENSP00000356224	P1

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89218 AN: 151748 Hom.: 26544 Cov.: 31

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.678

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.599

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

GnomAD4 genome AF: 0.588 AC: 89339 AN: 151868 Hom.: 26595 Cov.: 31 AF XY: 0.590 AC XY: 43748 AN XY: 74204

Gnomad4 AFR AF: 0.657

Gnomad4 AMR AF: 0.658

Gnomad4 ASJ AF: 0.579

Gnomad4 EAS AF: 0.690

Gnomad4 SAS AF: 0.677

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.538

Gnomad4 OTH AF: 0.602

Alfa AF: 0.556 Hom.: 15146

Bravo AF: 0.606

Asia WGS AF: 0.687 AC: 2388 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.0020
DANN	Benign	0.31

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs718527; hg19: chr6-152470136; COSMIC: COSV54938513; COSMIC: COSV54938513;