rs214959

Variant names:

• chr6-152381686-G-A
• rs214959
• NM_182961.4:c.8653-324C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-152381686-G-A
• chr6-152381686-G-C
• chr6-152381686-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.8653-324C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 378,674 control chromosomes in the GnomAD database, including 70,372 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.64 (33355 hom., cov: 31)
  • Exomes 𝑓: 0.56 (37017 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.740
• Publications: 6 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-AS1 (HGNC:40793): (SYNE1 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 6-152381686-G-A is Benign according to our data. Variant chr6-152381686-G-A is described in ClinVar as Benign. ClinVar VariationId is 683934.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.888 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.8653-324C>T		intron	N/A	NP_892006.3	Q8NF91-1
	SYNE1	NM_033071.5		c.8674-324C>T		intron	N/A	NP_149062.2	Q8NF91-4
	SYNE1-AS1	NR_120501.1		n.691G>A		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE1	ENST00000367255.10	TSL:1 MANE Select	c.8653-324C>T		intron	N/A	ENSP00000356224.5	Q8NF91-1
	SYNE1	ENST00000423061.6	TSL:1	c.8674-324C>T		intron	N/A	ENSP00000396024.1	A0A0C4DG40
	SYNE1	ENST00000454018.7	TSL:1	c.4-324C>T		intron	N/A	ENSP00000390858.4	A0A0C4DH48

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97493 AN: 151878 Hom.: 33301 Cov.: 31

Gnomad AFR AF: 0.895

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.608

GnomAD4 exome AF: 0.564 AC: 127850 AN: 226678 Hom.: 37017 AF XY: 0.569 AC XY: 68907 AN XY: 121004

African (AFR) AF: 0.900 AC: 6308 AN: 7010

American (AMR) AF: 0.519 AC: 5873 AN: 11312

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 3208 AN: 6288

East Asian (EAS) AF: 0.653 AC: 7709 AN: 11810

South Asian (SAS) AF: 0.620 AC: 21319 AN: 34398

European-Finnish (FIN) AF: 0.619 AC: 6544 AN: 10568

Middle Eastern (MID) AF: 0.623 AC: 528 AN: 848

European-Non Finnish (NFE) AF: 0.525 AC: 69365 AN: 132194

Other (OTH) AF: 0.571 AC: 6996 AN: 12250

GnomAD4 genome AF: 0.642 AC: 97596 AN: 151996 Hom.: 33355 Cov.: 31 AF XY: 0.644 AC XY: 47804 AN XY: 74276

African (AFR) AF: 0.895 AC: 37171 AN: 41524

American (AMR) AF: 0.526 AC: 8026 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 1780 AN: 3472

East Asian (EAS) AF: 0.646 AC: 3325 AN: 5146

South Asian (SAS) AF: 0.618 AC: 2975 AN: 4816

European-Finnish (FIN) AF: 0.637 AC: 6706 AN: 10528

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.526 AC: 35705 AN: 67930

Other (OTH) AF: 0.610 AC: 1288 AN: 2110

Alfa AF: 0.552 Hom.: 50251

Bravo AF: 0.645

Asia WGS AF: 0.624 AC: 2169 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	-0.89
CADD	Benign	4.4
DANN	Benign	0.66
PhyloP100		0.74
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: rs214959; hg19: chr6-152702821;