rs6908392

Variant names:

• chr6-152352012-G-A
• rs6908392
• NM_182961.4:c.11580+15C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-152352012-G-A
• chr6-152352012-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_182961.4(SYNE1):​c.11580+15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 1,611,640 control chromosomes in the GnomAD database, including 291,700 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (25249 hom., cov: 32)
  • Exomes 𝑓: 0.60 (266451 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -0.117
• Publications: 11 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 6-152352012-G-A is Benign according to our data. Variant chr6-152352012-G-A is described in ClinVar as Benign. ClinVar VariationId is 262154.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.604 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE1	NM_182961.4	MANE Select	c.11580+15C>T		intron	N/A	NP_892006.3
	SYNE1	NM_033071.5		c.11535+15C>T		intron	N/A	NP_149062.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE1	ENST00000367255.10	TSL:1 MANE Select	c.11580+15C>T		intron	N/A	ENSP00000356224.5
	SYNE1	ENST00000423061.6	TSL:1	c.11535+15C>T		intron	N/A	ENSP00000396024.1
	SYNE1	ENST00000471834.1	TSL:1	n.4718+15C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87282 AN: 151886 Hom.: 25231 Cov.: 32

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.589

GnomAD2 exomes AF: 0.584 AC: 144990 AN: 248276 AF XY: 0.582

Gnomad AFR exome AF: 0.503

Gnomad AMR exome AF: 0.602

Gnomad ASJ exome AF: 0.647

Gnomad EAS exome AF: 0.605

Gnomad FIN exome AF: 0.548

Gnomad NFE exome AF: 0.604

Gnomad OTH exome AF: 0.588

GnomAD4 exome AF: 0.603 AC: 880097 AN: 1459634 Hom.: 266451 Cov.: 35 AF XY: 0.600 AC XY: 436084 AN XY: 726236

African (AFR) AF: 0.494 AC: 16534 AN: 33436

American (AMR) AF: 0.604 AC: 26984 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 16931 AN: 26132

East Asian (EAS) AF: 0.640 AC: 25388 AN: 39688

South Asian (SAS) AF: 0.525 AC: 45160 AN: 85990

European-Finnish (FIN) AF: 0.546 AC: 28924 AN: 53002

Middle Eastern (MID) AF: 0.520 AC: 2839 AN: 5462

European-Non Finnish (NFE) AF: 0.613 AC: 681431 AN: 1110900

Other (OTH) AF: 0.595 AC: 35906 AN: 60316

GnomAD4 genome AF: 0.575 AC: 87345 AN: 152006 Hom.: 25249 Cov.: 32 AF XY: 0.571 AC XY: 42388 AN XY: 74278

African (AFR) AF: 0.508 AC: 21064 AN: 41466

American (AMR) AF: 0.612 AC: 9345 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2226 AN: 3472

East Asian (EAS) AF: 0.620 AC: 3195 AN: 5150

South Asian (SAS) AF: 0.535 AC: 2582 AN: 4824

European-Finnish (FIN) AF: 0.534 AC: 5629 AN: 10540

Middle Eastern (MID) AF: 0.493 AC: 144 AN: 292

European-Non Finnish (NFE) AF: 0.609 AC: 41399 AN: 67966

Other (OTH) AF: 0.591 AC: 1247 AN: 2110

Alfa AF: 0.599 Hom.: 78207

Bravo AF: 0.578

Asia WGS AF: 0.594 AC: 2067 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	2	Autosomal recessive ataxia, Beauce type (2)
-	-	2	Emery-Dreifuss muscular dystrophy 4, autosomal dominant (2)
-	-	1	Arthrogryposis multiplex congenita 3, myogenic type (1)
-	-	1	Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.3
DANN	Benign	0.20
PhyloP100		-0.12
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: rs6908392; hg19: chr6-152673147; COSMIC: COSV54935163;