rs2348080

chr6-152151525-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_182961.4(SYNE1):c.24450+28A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0406 in 1,613,058 control chromosomes in the GnomAD database, including 1,530 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.043 (171 hom., cov: 32)
  • Exomes 𝑓: 0.040 (1359 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.470

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 6-152151525-T-A is Benign according to our data. Variant chr6-152151525-T-A is described in ClinVar as [Benign]. Clinvar id is 262189.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0429 (6536/152242) while in subpopulation AMR AF= 0.0505 (772/15300). AF 95% confidence interval is 0.0475. There are 171 homozygotes in gnomad4. There are 3183 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 6516 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_001347702.2	c.915+28A>T		intron_variant		ENST00000354674.5
SYNE1	NM_182961.4	c.24450+28A>T		intron_variant		ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000354674.5	c.915+28A>T		intron_variant		5	NM_001347702.2
SYNE1	ENST00000367255.10	c.24450+28A>T		intron_variant		1	NM_182961.4	P1

Frequencies

GnomAD3 genomes AF: 0.0428 AC: 6516 AN: 152124 Hom.: 170 Cov.: 32

Gnomad AFR AF: 0.0461

Gnomad AMI AF: 0.0275

Gnomad AMR AF: 0.0507

Gnomad ASJ AF: 0.0926

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0193

Gnomad FIN AF: 0.0428

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0411

Gnomad OTH AF: 0.0578

GnomAD3 exomes AF: 0.0383 AC: 9565 AN: 249744 Hom.: 233 AF XY: 0.0378 AC XY: 5107 AN XY: 135158

Gnomad AFR exome AF: 0.0468

Gnomad AMR exome AF: 0.0332

Gnomad ASJ exome AF: 0.0882

Gnomad EAS exome AF: 0.000817

Gnomad SAS exome AF: 0.0194

Gnomad FIN exome AF: 0.0430

Gnomad NFE exome AF: 0.0440

Gnomad OTH exome AF: 0.0478

GnomAD4 exome AF: 0.0403 AC: 58928 AN: 1460816 Hom.: 1359 Cov.: 31 AF XY: 0.0398 AC XY: 28919 AN XY: 726644

Gnomad4 AFR exome AF: 0.0460

Gnomad4 AMR exome AF: 0.0345

Gnomad4 ASJ exome AF: 0.0933

Gnomad4 EAS exome AF: 0.000327

Gnomad4 SAS exome AF: 0.0189

Gnomad4 FIN exome AF: 0.0438

Gnomad4 NFE exome AF: 0.0417

Gnomad4 OTH exome AF: 0.0459

GnomAD4 genome AF: 0.0429 AC: 6536 AN: 152242 Hom.: 171 Cov.: 32 AF XY: 0.0428 AC XY: 3183 AN XY: 74456

Gnomad4 AFR AF: 0.0463

Gnomad4 AMR AF: 0.0505

Gnomad4 ASJ AF: 0.0926

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0191

Gnomad4 FIN AF: 0.0428

Gnomad4 NFE AF: 0.0411

Gnomad4 OTH AF: 0.0610

Alfa AF: 0.0498 Hom.: 37

Bravo AF: 0.0433

Asia WGS AF: 0.0360 AC: 124 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	3.2
Dann	Benign	0.34

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2348080; hg19: chr6-152472660;