6-152122254-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_182961.4(SYNE1):c.*182G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 873,974 control chromosomes in the GnomAD database, including 19,245 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4258 hom., cov: 33)

Exomes 𝑓: 0.20 ( 14987 hom. )

Consequence

SYNE1
NM_182961.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.129

Variant links:

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 links:

ESR1 (HGNC:3467): (estrogen receptor 1) This gene encodes an estrogen receptor and ligand-activated transcription factor. The canonical protein contains an N-terminal ligand-independent transactivation domain, a central DNA binding domain, a hinge domain, and a C-terminal ligand-dependent transactivation domain. The protein localizes to the nucleus where it may form either a homodimer or a heterodimer with estrogen receptor 2. The protein encoded by this gene regulates the transcription of many estrogen-inducible genes that play a role in growth, metabolism, sexual development, gestation, and other reproductive functions and is expressed in many non-reproductive tissues. The receptor encoded by this gene plays a key role in breast cancer, endometrial cancer, and osteoporosis. This gene is reported to have dozens of transcript variants due to the use of alternate promoters and alternative splicing, however, the full-length nature of many of these variants remain uncertain. [provided by RefSeq, Jul 2020]

ESR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 6-152122254-C-T is Benign according to our data. Variant chr6-152122254-C-T is described in ClinVar as [Benign]. Clinvar id is 355803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-152122254-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE1	NM_001347702.2 linkuse as main transcript	c.*182G>A		3_prime_UTR_variant	18/18	ENST00000354674.5
SYNE1	NM_182961.4 linkuse as main transcript	c.*182G>A		3_prime_UTR_variant	146/146	ENST00000367255.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE1	ENST00000354674.5 linkuse as main transcript	c.*182G>A		3_prime_UTR_variant	18/18	5	NM_001347702.2
SYNE1	ENST00000367255.10 linkuse as main transcript	c.*182G>A		3_prime_UTR_variant	146/146	1	NM_182961.4	P1	Q8NF91-1

Frequencies

GnomAD3 genomes

AF:

0.232

AC:

35269

AN:

152044

Hom.:

4258

Cov.:

show subpopulations

Gnomad AFR

AF:

0.299

Gnomad AMI

AF:

0.162

Gnomad AMR

AF:

0.200

Gnomad ASJ

AF:

0.184

Gnomad EAS

AF:

0.124

Gnomad SAS

AF:

0.109

Gnomad FIN

AF:

0.292

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.210

Gnomad OTH

AF:

0.217

GnomAD4 exome

AF:

0.199

AC:

143496

AN:

721814

Hom.:

14987

Cov.:

AF XY:

0.194

AC XY:

72182

AN XY:

371612

show subpopulations

Gnomad4 AFR exome

AF:

0.301

Gnomad4 AMR exome

AF:

0.201

Gnomad4 ASJ exome

AF:

0.183

Gnomad4 EAS exome

AF:

0.142

Gnomad4 SAS exome

AF:

0.110

Gnomad4 FIN exome

AF:

0.265

Gnomad4 NFE exome

AF:

0.205

Gnomad4 OTH exome

AF:

0.198

GnomAD4 genome

AF:

0.232

AC:

35288

AN:

152160

Hom.:

4258

Cov.:

AF XY:

0.230

AC XY:

17125

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.298

Gnomad4 AMR

AF:

0.200

Gnomad4 ASJ

AF:

0.184

Gnomad4 EAS

AF:

0.125

Gnomad4 SAS

AF:

0.109

Gnomad4 FIN

AF:

0.292

Gnomad4 NFE

AF:

0.210

Gnomad4 OTH

AF:

0.214

Alfa

AF:

0.200

Hom.:

3147

Bravo

AF:

0.231

Asia WGS

AF:

0.150

AC:

523

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2018

- -

Autosomal recessive ataxia, Beauce type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Emery-Dreifuss muscular dystrophy 4, autosomal dominant

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

Cadd

Benign

3.2

Dann

Benign

0.53

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over