17-4901883-G-A

Variant names:

• chr17-4901883-G-A
• rs111413308
• NM_001145536.2:c.*1350G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001145536.2(C17orf107):​c.*1350G>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 0.00685 in 1,215,460 control chromosomes in the GnomAD database, including 444 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (279 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (165 hom.)
• Consequence: C17orf107 NM_001145536.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.579
• Publications: 2 publications found

Genes affected

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

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 17-4901883-G-A is Benign according to our data. Variant chr17-4901883-G-A is described in ClinVar as Benign. ClinVar VariationId is 254900.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145536.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C17orf107	NM_001145536.2	MANE Select	c.*1350G>A		3_prime_UTR	Exon 3 of 3	NP_001139008.1
	CHRNE	NM_000080.4	MANE Select	c.500+49C>T		intron	N/A	NP_000071.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C17orf107	ENST00000381365.4	TSL:2 MANE Select	c.*1350G>A		3_prime_UTR	Exon 3 of 3	ENSP00000370770.3
	CHRNE	ENST00000649488.2	MANE Select	c.500+49C>T		intron	N/A	ENSP00000497829.1
	CHRNE	ENST00000649830.1		c.-434+49C>T		intron	N/A	ENSP00000496907.1

Frequencies

GnomAD3 genomes AF: 0.0337 AC: 4946 AN: 146694 Hom.: 272 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0159

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000856

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0161

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.0225

GnomAD2 exomes AF: 0.00890 AC: 2161 AN: 242944 AF XY: 0.00674

Gnomad AFR exome AF: 0.119

Gnomad AMR exome AF: 0.00883

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000459

Gnomad OTH exome AF: 0.00675

GnomAD4 exome AF: 0.00314 AC: 3356 AN: 1068652 Hom.: 165 Cov.: 28 AF XY: 0.00271 AC XY: 1478 AN XY: 544962

African (AFR) AF: 0.0902 AC: 2304 AN: 25542

American (AMR) AF: 0.00959 AC: 413 AN: 43084

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22804

East Asian (EAS) AF: 0.00 AC: 0 AN: 36030

South Asian (SAS) AF: 0.000397 AC: 31 AN: 78144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49212

Middle Eastern (MID) AF: 0.00549 AC: 20 AN: 3646

European-Non Finnish (NFE) AF: 0.000268 AC: 205 AN: 764032

Other (OTH) AF: 0.00830 AC: 383 AN: 46158

GnomAD4 genome AF: 0.0339 AC: 4975 AN: 146808 Hom.: 279 Cov.: 32 AF XY: 0.0324 AC XY: 2316 AN XY: 71552

African (AFR) AF: 0.117 AC: 4646 AN: 39542

American (AMR) AF: 0.0158 AC: 237 AN: 14974

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3432

East Asian (EAS) AF: 0.00 AC: 0 AN: 4908

South Asian (SAS) AF: 0.000642 AC: 3 AN: 4674

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9688

Middle Eastern (MID) AF: 0.0172 AC: 5 AN: 290

European-Non Finnish (NFE) AF: 0.000573 AC: 38 AN: 66356

Other (OTH) AF: 0.0223 AC: 46 AN: 2064

Alfa AF: 0.00241 Hom.: 3

Bravo AF: 0.0386

Asia WGS AF: 0.00898 AC: 31 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Oct 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.79
PhyloP100		0.58
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs111413308; hg19: chr17-4805178;