17-4900778-G-C

Variant names:

• chr17-4900778-G-C
• rs12942540
• NM_001145536.2:c.*245G>C

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.*245G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,608,764 control chromosomes in the GnomAD database, including 16,889 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2132 hom., cov: 33)
  • Exomes 𝑓: 0.14 (14757 hom.)
• Consequence: C17orf107 NM_001145536.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.232
• Publications: 10 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: AR, AD Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• congenital myasthenic syndrome 4B

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• 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=-0.81).
• BP6: Variant 17-4900778-G-C is Benign according to our data. Variant chr17-4900778-G-C is described in ClinVar as Benign. ClinVar VariationId is 254903.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C17orf107	NM_001145536.2	MANE Select	c.*245G>C		3_prime_UTR	Exon 3 of 3	NP_001139008.1	Q6ZR85
	CHRNE	NM_000080.4	MANE Select	c.917+15C>G		intron	N/A	NP_000071.1	Q04844

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C17orf107	ENST00000381365.4	TSL:2 MANE Select	c.*245G>C		3_prime_UTR	Exon 3 of 3	ENSP00000370770.3	Q6ZR85
	C17orf107	ENST00000521575.1	TSL:1	c.*612G>C		3_prime_UTR	Exon 2 of 2	ENSP00000429241.1	E5RJ01
	CHRNE	ENST00000649488.2	MANE Select	c.917+15C>G		intron	N/A	ENSP00000497829.1	Q04844

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24557 AN: 152162 Hom.: 2132 Cov.: 33

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.0884

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.175

GnomAD2 exomes AF: 0.143 AC: 34080 AN: 238054 AF XY: 0.143

Gnomad AFR exome AF: 0.214

Gnomad AMR exome AF: 0.158

Gnomad ASJ exome AF: 0.143

Gnomad EAS exome AF: 0.0844

Gnomad FIN exome AF: 0.129

Gnomad NFE exome AF: 0.139

Gnomad OTH exome AF: 0.155

GnomAD4 exome AF: 0.140 AC: 204526 AN: 1456484 Hom.: 14757 Cov.: 32 AF XY: 0.141 AC XY: 101812 AN XY: 724428

African (AFR) AF: 0.216 AC: 7200 AN: 33290

American (AMR) AF: 0.161 AC: 7073 AN: 44006

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 3767 AN: 26052

East Asian (EAS) AF: 0.117 AC: 4609 AN: 39450

South Asian (SAS) AF: 0.149 AC: 12805 AN: 85804

European-Finnish (FIN) AF: 0.132 AC: 6990 AN: 52990

Middle Eastern (MID) AF: 0.203 AC: 1168 AN: 5740

European-Non Finnish (NFE) AF: 0.137 AC: 152182 AN: 1108982

Other (OTH) AF: 0.145 AC: 8732 AN: 60170

GnomAD4 genome AF: 0.161 AC: 24575 AN: 152280 Hom.: 2132 Cov.: 33 AF XY: 0.160 AC XY: 11910 AN XY: 74454

African (AFR) AF: 0.215 AC: 8957 AN: 41566

American (AMR) AF: 0.174 AC: 2662 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 537 AN: 3472

East Asian (EAS) AF: 0.0886 AC: 457 AN: 5160

South Asian (SAS) AF: 0.149 AC: 717 AN: 4828

European-Finnish (FIN) AF: 0.121 AC: 1279 AN: 10606

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9415 AN: 68026

Other (OTH) AF: 0.172 AC: 363 AN: 2116

Alfa AF: 0.146 Hom.: 326

Bravo AF: 0.169

Asia WGS AF: 0.132 AC: 460 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	Congenital myasthenic syndrome 4A (2)
-	-	1	Congenital myasthenic syndrome (1)
-	-	1	Congenital myasthenic syndrome 4B (1)
-	-	1	Congenital myasthenic syndrome 4C (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.1
DANN	Benign	0.50
PhyloP100		0.23
Mutation Taster		=19/81	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs12942540;

hg19: chr17-4804073;

COSMIC: COSV53417534;

COSMIC: COSV53417534;