rs2813484

Variant names:

• chr6-152142767-A-G
• rs2813484
• NM_182961.4:c.25119+856T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182961.4(SYNE1):​c.25119+856T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 152,084 control chromosomes in the GnomAD database, including 10,881 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 0.36 (10881 hom., cov: 33)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.338
• Publications: 5 publications found

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]

SYNE1 Gene-Disease associations (from GenCC):

• autosomal recessive ataxia, Beauce type

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Orphanet, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
• arthrogryposis multiplex congenita 3, myogenic type

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Emery-Dreifuss muscular dystrophy 4, autosomal dominant

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina
• autosomal dominant Emery-Dreifuss muscular dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive myogenic arthrogryposis multiplex congenita

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000300811 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4	c.25119+856T>C		intron_variant	Intron 138 of 145	ENST00000367255.10	NP_892006.3
SYNE1	NM_001347702.2	c.1653+856T>C		intron_variant	Intron 10 of 17	ENST00000354674.5	NP_001334631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10	c.25119+856T>C		intron_variant	Intron 138 of 145	1	NM_182961.4	ENSP00000356224.5
SYNE1	ENST00000354674.5	c.1653+856T>C		intron_variant	Intron 10 of 17	5	NM_001347702.2	ENSP00000346701.4

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54689 AN: 151966 Hom.: 10876 Cov.: 33

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.360 AC: 54742 AN: 152084 Hom.: 10881 Cov.: 33 AF XY: 0.359 AC XY: 26730 AN XY: 74366

African (AFR) AF: 0.520 AC: 21576 AN: 41462

American (AMR) AF: 0.430 AC: 6565 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1227 AN: 3468

East Asian (EAS) AF: 0.307 AC: 1591 AN: 5176

South Asian (SAS) AF: 0.394 AC: 1901 AN: 4820

European-Finnish (FIN) AF: 0.174 AC: 1843 AN: 10604

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18896 AN: 67960

Other (OTH) AF: 0.378 AC: 799 AN: 2112

Alfa AF: 0.334 Hom.: 1496

Bravo AF: 0.388

Asia WGS AF: 0.343 AC: 1190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.2
DANN	Benign	0.60
PhyloP100		0.34
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2813484; hg19: chr6-152463902;