17-4897868-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_153827.5(MINK1):c.*581C>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 0.371 in 149,182 control chromosomes in the GnomAD database, including 10,488 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 10451 hom., cov: 25)

Exomes 𝑓: 0.32 ( 37 hom. )

Consequence

MINK1
NM_153827.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.73

Publications

13 publications found

Variant links:

Genes affected

MINK1 (HGNC:17565): (misshapen like kinase 1) This gene encodes a serine/threonine kinase belonging to the germinal center kinase (GCK) family. The protein is structurally similar to the kinases that are related to NIK and may belong to a distinct subfamily of NIK-related kinases within the GCK family. Studies of the mouse homolog indicate an up-regulation of expression in the course of postnatal mouse cerebral development and activation of the cJun N-terminal kinase (JNK) and the p38 pathways. [provided by RefSeq, Mar 2016]

MINK1 links:

CHRNE (HGNC:1966): (cholinergic receptor nicotinic epsilon subunit) Acetylcholine receptors at mature mammalian neuromuscular junctions are pentameric protein complexes composed of four subunits in the ratio of two alpha subunits to one beta, one epsilon, and one delta subunit. The acetylcholine receptor changes subunit composition shortly after birth when the epsilon subunit replaces the gamma subunit seen in embryonic receptors. Mutations in the epsilon subunit are associated with congenital myasthenic syndrome. [provided by RefSeq, Sep 2009]

CHRNE Gene-Disease associations (from GenCC):

congenital myasthenic syndrome
Inheritance: AR Classification: DEFINITIVE Submitted by: Illumina
congenital myasthenic syndrome 4A
Inheritance: AD, AR Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia
congenital myasthenic syndrome 4B
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia
congenital myasthenic syndrome 4C
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
postsynaptic congenital myasthenic syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CHRNE links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 17-4897868-C-A is Benign according to our data. Variant chr17-4897868-C-A is described in ClinVar as [Benign]. Clinvar id is 323948.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MINK1	NM_153827.5 link	c.*581C>A		3_prime_UTR_variant	Exon 32 of 32	ENST00000355280.11	NP_722549.2	Q8N4C8-1
CHRNE	NM_000080.4 link	c.*868G>T		3_prime_UTR_variant	Exon 12 of 12	ENST00000649488.2	NP_000071.1	Q04844

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MINK1	ENST00000355280.11 link	c.*581C>A		3_prime_UTR_variant	Exon 32 of 32	1	NM_153827.5	ENSP00000347427.6		Q8N4C8-1
CHRNE	ENST00000649488.2 link	c.*868G>T		3_prime_UTR_variant	Exon 12 of 12		NM_000080.4	ENSP00000497829.1		Q04844

Frequencies

GnomAD3 genomes

AF:

0.371

AC:

55168

AN:

148516

Hom.:

10439

Cov.:

show subpopulations

Gnomad AFR

AF:

0.400

Gnomad AMI

AF:

0.296

Gnomad AMR

AF:

0.365

Gnomad ASJ

AF:

0.380

Gnomad EAS

AF:

0.551

Gnomad SAS

AF:

0.580

Gnomad FIN

AF:

0.414

Gnomad MID

AF:

0.407

Gnomad NFE

AF:

0.323

Gnomad OTH

AF:

0.356

GnomAD4 exome

AF:

0.316

AC:

173

AN:

548

Hom.:

Cov.:

AF XY:

0.281

AC XY:

AN XY:

306

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.594

AC:

AN:

European-Finnish (FIN)

AF:

0.401

AC:

AN:

222

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.225

AC:

AN:

280

Other (OTH)

AF:

0.125

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.372

AC:

55225

AN:

148634

Hom.:

10451

Cov.:

AF XY:

0.381

AC XY:

27596

AN XY:

72364

show subpopulations

African (AFR)

AF:

0.400

AC:

16084

AN:

40176

American (AMR)

AF:

0.365

AC:

5474

AN:

15012

Ashkenazi Jewish (ASJ)

AF:

0.380

AC:

1309

AN:

3446

East Asian (EAS)

AF:

0.551

AC:

2717

AN:

4928

South Asian (SAS)

AF:

0.579

AC:

2656

AN:

4584

European-Finnish (FIN)

AF:

0.414

AC:

4154

AN:

10024

Middle Eastern (MID)

AF:

0.390

AC:

113

AN:

290

European-Non Finnish (NFE)

AF:

0.323

AC:

21719

AN:

67200

Other (OTH)

AF:

0.353

AC:

733

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

Heterozygous variant carriers

1605

3209

4814

6418

8023

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.312

Hom.:

2944

Asia WGS

AF:

0.563

AC:

1956

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Congenital myasthenic syndrome

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.042

(source)

DANN

Benign

0.33

PhyloP100

-2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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17-4897868-C-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over