chr17-4901607-G-A

Variant names:

• chr17-4901607-G-A
• rs33970119
• NM_000080.4:c.519C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000080.4(CHRNE):​c.519C>T​(p.Ala173Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0518 in 1,613,756 control chromosomes in the GnomAD database, including 2,544 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.039 (169 hom., cov: 33)
  • Exomes 𝑓: 0.053 (2375 hom.)
• Consequence: CHRNE NM_000080.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.314
• Publications: 9 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 17-4901607-G-A is Benign according to our data. Variant chr17-4901607-G-A is described in ClinVar as Benign. ClinVar VariationId is 128767.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.314 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNE	NM_000080.4	c.519C>T	p.Ala173Ala	synonymous_variant	Exon 6 of 12	ENST00000649488.2	NP_000071.1
C17orf107	NM_001145536.2	c.*1074G>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000381365.4	NP_001139008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNE	ENST00000649488.2	c.519C>T	p.Ala173Ala	synonymous_variant	Exon 6 of 12		NM_000080.4	ENSP00000497829.1
C17orf107	ENST00000381365.4	c.*1074G>A		3_prime_UTR_variant	Exon 3 of 3	2	NM_001145536.2	ENSP00000370770.3

Frequencies

GnomAD3 genomes AF: 0.0389 AC: 5917 AN: 152168 Hom.: 169 Cov.: 33

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.0387

Gnomad ASJ AF: 0.0291

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.0110

Gnomad FIN AF: 0.0366

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0609

Gnomad OTH AF: 0.0392

GnomAD2 exomes AF: 0.0372 AC: 9299 AN: 250084 AF XY: 0.0375

Gnomad AFR exome AF: 0.00905

Gnomad AMR exome AF: 0.0241

Gnomad ASJ exome AF: 0.0291

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0398

Gnomad NFE exome AF: 0.0585

Gnomad OTH exome AF: 0.0419

GnomAD4 exome AF: 0.0531 AC: 77599 AN: 1461470 Hom.: 2375 Cov.: 32 AF XY: 0.0518 AC XY: 37676 AN XY: 727052

African (AFR) AF: 0.00878 AC: 294 AN: 33476

American (AMR) AF: 0.0259 AC: 1157 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0279 AC: 729 AN: 26132

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39700

South Asian (SAS) AF: 0.0103 AC: 892 AN: 86252

European-Finnish (FIN) AF: 0.0399 AC: 2130 AN: 53364

Middle Eastern (MID) AF: 0.0279 AC: 161 AN: 5768

European-Non Finnish (NFE) AF: 0.0623 AC: 69269 AN: 1111676

Other (OTH) AF: 0.0491 AC: 2962 AN: 60382

GnomAD4 genome AF: 0.0388 AC: 5914 AN: 152286 Hom.: 169 Cov.: 33 AF XY: 0.0368 AC XY: 2741 AN XY: 74460

African (AFR) AF: 0.0109 AC: 454 AN: 41562

American (AMR) AF: 0.0386 AC: 590 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0291 AC: 101 AN: 3470

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5170

South Asian (SAS) AF: 0.0114 AC: 55 AN: 4830

European-Finnish (FIN) AF: 0.0366 AC: 389 AN: 10620

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0609 AC: 4144 AN: 68018

Other (OTH) AF: 0.0388 AC: 82 AN: 2112

Alfa AF: 0.0519 Hom.: 256

Bravo AF: 0.0391

Asia WGS AF: 0.00462 AC: 16 AN: 3478

EpiCase AF: 0.0629

EpiControl AF: 0.0609

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Oct 12, 2016

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. -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Nov 13, 2024

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Congenital myasthenic syndrome Benign:2

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 13, 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. -

Congenital myasthenic syndrome 4A Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	13
DANN	Benign	0.91
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs33970119; hg19: chr17-4804902;