rs17082180

Variant names:

• chr6-152136958-G-A
• rs17082180
• NM_182961.4:c.25459-140C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-152136958-G-A
• chr6-152136958-G-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.25459-140C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 824,566 control chromosomes in the GnomAD database, including 8,112 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1463 hom., cov: 32)
  • Exomes 𝑓: 0.13 (6649 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.276
• Publications: 4 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 6-152136958-G-A is Benign according to our data. Variant chr6-152136958-G-A is described in ClinVar as Benign. ClinVar VariationId is 1295984.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4	c.25459-140C>T		intron_variant	Intron 140 of 145	ENST00000367255.10	NP_892006.3
SYNE1	NM_001347702.2	c.1993-140C>T		intron_variant	Intron 12 of 17	ENST00000354674.5	NP_001334631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10	c.25459-140C>T		intron_variant	Intron 140 of 145	1	NM_182961.4	ENSP00000356224.5
SYNE1	ENST00000354674.5	c.1993-140C>T		intron_variant	Intron 12 of 17	5	NM_001347702.2	ENSP00000346701.4

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20539 AN: 151882 Hom.: 1450 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.0708

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.0599

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.104

GnomAD4 exome AF: 0.135 AC: 90697 AN: 672566 Hom.: 6649 AF XY: 0.135 AC XY: 48047 AN XY: 356452

African (AFR) AF: 0.146 AC: 2612 AN: 17904

American (AMR) AF: 0.0542 AC: 1868 AN: 34470

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 2209 AN: 20224

East Asian (EAS) AF: 0.0892 AC: 2924 AN: 32780

South Asian (SAS) AF: 0.124 AC: 7882 AN: 63386

European-Finnish (FIN) AF: 0.181 AC: 6284 AN: 34720

Middle Eastern (MID) AF: 0.0643 AC: 205 AN: 3190

European-Non Finnish (NFE) AF: 0.145 AC: 62380 AN: 431372

Other (OTH) AF: 0.126 AC: 4333 AN: 34520

GnomAD4 genome AF: 0.136 AC: 20599 AN: 152000 Hom.: 1463 Cov.: 32 AF XY: 0.134 AC XY: 9956 AN XY: 74276

African (AFR) AF: 0.145 AC: 6008 AN: 41464

American (AMR) AF: 0.0706 AC: 1079 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 379 AN: 3472

East Asian (EAS) AF: 0.0601 AC: 311 AN: 5178

South Asian (SAS) AF: 0.129 AC: 621 AN: 4808

European-Finnish (FIN) AF: 0.177 AC: 1862 AN: 10526

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 9967 AN: 67960

Other (OTH) AF: 0.110 AC: 232 AN: 2104

Alfa AF: 0.146 Hom.: 1373

Bravo AF: 0.124

Asia WGS AF: 0.140 AC: 491 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.26
PhyloP100		-0.28
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: rs17082180; hg19: chr6-152458093; COSMIC: COSV55015762;