rs7762904

Variant names:

• chr6-152347493-C-G
• rs7762904
• NM_182961.4:c.11902-258G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-152347493-C-G
• chr6-152347493-C-A

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.11902-258G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 151,786 control chromosomes in the GnomAD database, including 24,705 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.57 (24705 hom., cov: 30)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.36
• 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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 6-152347493-C-G is Benign according to our data. Variant chr6-152347493-C-G is described in ClinVar as Benign. ClinVar VariationId is 683943.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.637 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.11902-258G>C		intron	N/A	NP_892006.3	Q8NF91-1
	SYNE1	NM_033071.5		c.11689-258G>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.11902-258G>C		intron	N/A	ENSP00000356224.5	Q8NF91-1
	SYNE1	ENST00000423061.6	TSL:1	c.11689-258G>C		intron	N/A	ENSP00000396024.1	A0A0C4DG40
	SYNE1	ENST00000471834.1	TSL:1	n.5040-258G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85766 AN: 151668 Hom.: 24692 Cov.: 30

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.649

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.585

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

GnomAD4 genome AF: 0.565 AC: 85821 AN: 151786 Hom.: 24705 Cov.: 30 AF XY: 0.561 AC XY: 41610 AN XY: 74164

African (AFR) AF: 0.458 AC: 18942 AN: 41360

American (AMR) AF: 0.608 AC: 9279 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.649 AC: 2249 AN: 3468

East Asian (EAS) AF: 0.656 AC: 3384 AN: 5162

South Asian (SAS) AF: 0.530 AC: 2550 AN: 4810

European-Finnish (FIN) AF: 0.537 AC: 5635 AN: 10490

Middle Eastern (MID) AF: 0.500 AC: 146 AN: 292

European-Non Finnish (NFE) AF: 0.617 AC: 41879 AN: 67926

Other (OTH) AF: 0.587 AC: 1239 AN: 2110

Alfa AF: 0.455 Hom.: 1242

Bravo AF: 0.567

Asia WGS AF: 0.597 AC: 2078 AN: 3474

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	-0.85
CADD	Benign	0.38
DANN	Benign	0.45
PhyloP100		-2.4
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: rs7762904; hg19: chr6-152668628;