6-152469438-G-T

Position:

• chr6-152469438-G-T

Variant summary

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

The NM_182961.4(SYNE1):​c.1632+2159C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 151,618 control chromosomes in the GnomAD database, including 18,037 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 0.46 (18037 hom., cov: 30)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.775

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 = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_182961.4	c.1632+2159C>A		intron_variant		ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000367255.10	c.1632+2159C>A		intron_variant		1	NM_182961.4	P1

Frequencies

GnomAD3 genomes AF: 0.461 AC: 69843 AN: 151500 Hom.: 18011 Cov.: 30

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.461 AC: 69917 AN: 151618 Hom.: 18037 Cov.: 30 AF XY: 0.461 AC XY: 34161 AN XY: 74084

Gnomad4 AFR AF: 0.682

Gnomad4 AMR AF: 0.363

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.756

Gnomad4 SAS AF: 0.495

Gnomad4 FIN AF: 0.335

Gnomad4 NFE AF: 0.350

Gnomad4 OTH AF: 0.452

Alfa AF: 0.377 Hom.: 11657

Bravo AF: 0.474

Asia WGS AF: 0.589 AC: 2049 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.32
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: rs9371601; hg19: chr6-152790573;