rs2813486

Variant names:

• chr6-152145300-A-G
• rs2813486
• NM_182961.4:c.24977-1535T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-152145300-A-G
• chr6-152145300-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_182961.4(SYNE1):​c.24977-1535T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 658,770 control chromosomes in the GnomAD database, including 41,506 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.37 (10818 hom., cov: 33)
  • Exomes 𝑓: 0.34 (30688 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.822
• Publications: 2 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: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics, Orphanet, PanelApp Australia, G2P
• Emery-Dreifuss muscular dystrophy 4, autosomal dominant

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Illumina, Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• arthrogryposis multiplex congenita 3, myogenic type

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 6-152145300-A-G is Benign according to our data. Variant chr6-152145300-A-G is described in ClinVar as Benign. ClinVar VariationId is 670215.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182961.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE1	NM_182961.4	MANE Select	c.24977-1535T>C		intron	N/A	NP_892006.3	Q8NF91-1
	SYNE1	NM_001347702.2	MANE Plus Clinical	c.1510+187T>C		intron	N/A	NP_001334631.1	F8WAI0
	SYNE1	NM_033071.5		c.24832+187T>C		intron	N/A	NP_149062.2	Q8NF91-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE1	ENST00000367255.10	TSL:1 MANE Select	c.24977-1535T>C		intron	N/A	ENSP00000356224.5	Q8NF91-1
	SYNE1	ENST00000354674.5	TSL:5 MANE Plus Clinical	c.1510+187T>C		intron	N/A	ENSP00000346701.4	F8WAI0
	SYNE1	ENST00000423061.6	TSL:1	c.24832+187T>C		intron	N/A	ENSP00000396024.1	A0A0C4DG40

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56213 AN: 151724 Hom.: 10804 Cov.: 33

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.411

GnomAD4 exome AF: 0.340 AC: 172454 AN: 506930 Hom.: 30688 Cov.: 5 AF XY: 0.344 AC XY: 93716 AN XY: 272094

African (AFR) AF: 0.443 AC: 6039 AN: 13630

American (AMR) AF: 0.490 AC: 12738 AN: 26008

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 6651 AN: 16392

East Asian (EAS) AF: 0.309 AC: 9609 AN: 31064

South Asian (SAS) AF: 0.413 AC: 22041 AN: 53396

European-Finnish (FIN) AF: 0.217 AC: 8052 AN: 37134

Middle Eastern (MID) AF: 0.400 AC: 855 AN: 2136

European-Non Finnish (NFE) AF: 0.322 AC: 96483 AN: 299204

Other (OTH) AF: 0.357 AC: 9986 AN: 27966

GnomAD4 genome AF: 0.371 AC: 56272 AN: 151840 Hom.: 10818 Cov.: 33 AF XY: 0.370 AC XY: 27501 AN XY: 74244

African (AFR) AF: 0.446 AC: 18461 AN: 41354

American (AMR) AF: 0.469 AC: 7157 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1413 AN: 3466

East Asian (EAS) AF: 0.311 AC: 1603 AN: 5158

South Asian (SAS) AF: 0.408 AC: 1969 AN: 4824

European-Finnish (FIN) AF: 0.215 AC: 2278 AN: 10572

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.326 AC: 22132 AN: 67910

Other (OTH) AF: 0.413 AC: 868 AN: 2104

Alfa AF: 0.351 Hom.: 1198

Bravo AF: 0.395

Asia WGS AF: 0.373 AC: 1296 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.2
DANN	Benign	0.46
PhyloP100		0.82
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: rs2813486; hg19: chr6-152466435; COSMIC: COSV55114739; COSMIC: COSV55114739;