rs1744380

Variant names:

• chr6-152621686-G-A
• rs1744380
• NM_182961.4:c.67+6579C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-152621686-G-A
• chr6-152621686-G-T

Variant summary

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

The ENST00000367255.10(SYNE1):​c.67+6579C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 151,216 control chromosomes in the GnomAD database, including 38,365 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 0.71 (38365 hom., cov: 31)
• Consequence: SYNE1 ENST00000367255.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.696
• 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: 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000367255.10. 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.67+6579C>T		intron	N/A	NP_892006.3
	SYNE1	NM_033071.5		c.67+6579C>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.67+6579C>T		intron	N/A	ENSP00000356224.5
	SYNE1	ENST00000423061.6	TSL:1	c.67+6579C>T		intron	N/A	ENSP00000396024.1
	SYNE1	ENST00000466159.6	TSL:1	c.67+6579C>T		intron	N/A	ENSP00000446021.1

Frequencies

GnomAD3 genomes AF: 0.712 AC: 107615 AN: 151098 Hom.: 38355 Cov.: 31

Gnomad AFR AF: 0.696

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.817

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.697

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.729

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

GnomAD4 genome AF: 0.712 AC: 107671 AN: 151216 Hom.: 38365 Cov.: 31 AF XY: 0.707 AC XY: 52211 AN XY: 73844

African (AFR) AF: 0.697 AC: 28699 AN: 41198

American (AMR) AF: 0.701 AC: 10674 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.691 AC: 2388 AN: 3458

East Asian (EAS) AF: 0.816 AC: 4197 AN: 5142

South Asian (SAS) AF: 0.636 AC: 3059 AN: 4808

European-Finnish (FIN) AF: 0.661 AC: 6937 AN: 10492

Middle Eastern (MID) AF: 0.692 AC: 202 AN: 292

European-Non Finnish (NFE) AF: 0.731 AC: 49395 AN: 67612

Other (OTH) AF: 0.729 AC: 1529 AN: 2096

Alfa AF: 0.702 Hom.: 7252

Bravo AF: 0.720

Asia WGS AF: 0.698 AC: 2430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.094
DANN	Benign	0.53
PhyloP100		-0.70
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: rs1744380; hg19: chr6-152942821;