rs3818110

Variant names:

• chr6-152139926-G-A
• rs3818110
• NM_182961.4:c.25458+24C>T

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.25458+24C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 1,610,822 control chromosomes in the GnomAD database, including 128,689 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14404 hom., cov: 31)
  • Exomes 𝑓: 0.39 (114285 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.287

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 6-152139926-G-A is Benign according to our data. Variant chr6-152139926-G-A is described in ClinVar as [Benign]. Clinvar id is 262193.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4	c.25458+24C>T		intron_variant	Intron 140 of 145	ENST00000367255.10	NP_892006.3
SYNE1	NM_001347702.2	c.1992+24C>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.25458+24C>T		intron_variant	Intron 140 of 145	1	NM_182961.4	ENSP00000356224.5
SYNE1	ENST00000354674.5	c.1992+24C>T		intron_variant	Intron 12 of 17	5	NM_001347702.2	ENSP00000346701.4

Frequencies

GnomAD3 genomes AF: 0.429 AC: 64863 AN: 151290 Hom.: 14403 Cov.: 31

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.468

GnomAD2 exomes AF: 0.408 AC: 101697 AN: 249532 AF XY: 0.404

Gnomad AFR exome AF: 0.529

Gnomad AMR exome AF: 0.532

Gnomad ASJ exome AF: 0.504

Gnomad EAS exome AF: 0.299

Gnomad FIN exome AF: 0.248

Gnomad NFE exome AF: 0.379

Gnomad OTH exome AF: 0.423

GnomAD4 exome AF: 0.392 AC: 571844 AN: 1459412 Hom.: 114285 Cov.: 35 AF XY: 0.393 AC XY: 285575 AN XY: 726014

Gnomad4 AFR exome AF: 0.524 AC: 17524 AN: 33416

Gnomad4 AMR exome AF: 0.532 AC: 23769 AN: 44650

Gnomad4 ASJ exome AF: 0.509 AC: 13299 AN: 26128

Gnomad4 EAS exome AF: 0.308 AC: 12240 AN: 39684

Gnomad4 SAS exome AF: 0.450 AC: 38745 AN: 86148

Gnomad4 FIN exome AF: 0.249 AC: 13300 AN: 53356

Gnomad4 NFE exome AF: 0.384 AC: 426272 AN: 1111318

Gnomad4 Remaining exome AF: 0.407 AC: 24489 AN: 60198

GnomAD4 genome AF: 0.429 AC: 64914 AN: 151410 Hom.: 14404 Cov.: 31 AF XY: 0.425 AC XY: 31449 AN XY: 74000

Gnomad4 AFR AF: 0.525 AC: 0.52524 AN: 0.52524

Gnomad4 AMR AF: 0.498 AC: 0.498293 AN: 0.498293

Gnomad4 ASJ AF: 0.501 AC: 0.501442 AN: 0.501442

Gnomad4 EAS AF: 0.309 AC: 0.309002 AN: 0.309002

Gnomad4 SAS AF: 0.437 AC: 0.437135 AN: 0.437135

Gnomad4 FIN AF: 0.245 AC: 0.24483 AN: 0.24483

Gnomad4 NFE AF: 0.387 AC: 0.387139 AN: 0.387139

Gnomad4 OTH AF: 0.467 AC: 0.466667 AN: 0.466667

Alfa AF: 0.402 Hom.: 5978

Bravo AF: 0.458

Asia WGS AF: 0.363 AC: 1260 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Jun 18, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.90
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3818110; hg19: chr6-152461061; COSMIC: COSV54896481;