17-4902022-G-T

Position:

chr17-4902022-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM1BP4_ModerateBP6_Moderate

The NM_000080.4(CHRNE):c.410C>A(p.Thr137Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000458 in 1,613,992 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000026 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

CHRNE
NM_000080.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.336

Variant links:

Genes affected

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 links:

C17orf107 (HGNC:37238): (chromosome 17 open reading frame 107)

C17orf107 links:

CHRNE (HGNC:):

CHRNE links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM1

In a topological_domain Extracellular (size 218) in uniprot entity ACHE_HUMAN there are 22 pathogenic changes around while only 0 benign (100%) in NM_000080.4

BP4

Computational evidence support a benign effect (MetaRNN=0.10154551).

BP6

Variant 17-4902022-G-T is Benign according to our data. Variant chr17-4902022-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 581033.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNE	NM_000080.4 linkuse as main transcript	c.410C>A	p.Thr137Lys	missense_variant	5/12	ENST00000649488.2	NP_000071.1	Q04844
C17orf107	NM_001145536.2 linkuse as main transcript	c.*1489G>T		3_prime_UTR_variant	3/3	ENST00000381365.4	NP_001139008.1	Q6ZR85

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CHRNE	ENST00000649488.2 linkuse as main transcript	c.410C>A	p.Thr137Lys	missense_variant	5/12		NM_000080.4	ENSP00000497829.1	Q04844
C17orf107	ENST00000381365.4 linkuse as main transcript	c.*1489G>T		3_prime_UTR_variant	3/3	2	NM_001145536.2	ENSP00000370770.3	Q6ZR85
CHRNE	ENST00000649830.1 linkuse as main transcript	c.-524C>A		5_prime_UTR_variant	5/11			ENSP00000496907.1	A0A3B3IRM1
CHRNE	ENST00000575637.1 linkuse as main transcript	n.231C>A		non_coding_transcript_exon_variant	4/6	3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000996

AC:

AN:

250914

Hom.:

AF XY:

0.000133

AC XY:

AN XY:

135706

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000817

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000479

AC:

AN:

1461748

Hom.:

Cov.:

AF XY:

0.0000633

AC XY:

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000800

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000827

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.000165

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Congenital myasthenic syndrome 4A

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 30, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.42

CADD

Benign

9.7

DANN

Benign

0.73

DEOGEN2

Benign

0.19

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.15

.;T

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

1.5

L;L

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.81

N;.

REVEL

Benign

0.25

Sift

Benign

0.33

T;.

Sift4G

Benign

0.39

T;.

Polyphen

0.29

B;B

Vest4

0.29

MutPred

0.37

Gain of methylation at T137 (P = 0.0189);Gain of methylation at T137 (P = 0.0189);

MVP

0.70

MPC

0.24

ClinPred

0.069

GERP RS

-2.7

Varity_R

0.12

gMVP

0.61

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

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