rs201470386

Variant names:

• chr17-4901893-C-T
• rs201470386
• NM_001145536.2:c.*1360C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-4901893-C-T
• chr17-4901893-C-A
• chr17-4901893-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001145536.2(C17orf107):​c.*1360C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00205 in 1,607,600 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (25 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (35 hom.)
• Consequence: C17orf107 NM_001145536.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0550
• Publications: 0 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: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• congenital myasthenic syndrome 4B

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• 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=-0.82).
• BP6: Variant 17-4901893-C-T is Benign according to our data. Variant chr17-4901893-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 254899.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0102 (1541/151474) while in subpopulation AFR AF = 0.0358 (1463/40816). AF 95% confidence interval is 0.0343. There are 25 homozygotes in GnomAd4. There are 710 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 25 AR gene

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.*1360C>T		3_prime_UTR	Exon 3 of 3	NP_001139008.1	Q6ZR85
	CHRNE	NM_000080.4	MANE Select	c.500+39G>A		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.*1360C>T		3_prime_UTR	Exon 3 of 3	ENSP00000370770.3	Q6ZR85
	CHRNE	ENST00000649488.2	MANE Select	c.500+39G>A		intron	N/A	ENSP00000497829.1	Q04844
	C17orf107	ENST00000861085.1		c.*1360C>T		3_prime_UTR	Exon 3 of 3	ENSP00000531144.1

Frequencies

GnomAD3 genomes AF: 0.0102 AC: 1539 AN: 151364 Hom.: 25 Cov.: 32

Gnomad AFR AF: 0.0359

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00328

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.00336

GnomAD2 exomes AF: 0.00281 AC: 695 AN: 247416 AF XY: 0.00212

Gnomad AFR exome AF: 0.0362

Gnomad AMR exome AF: 0.00229

Gnomad ASJ exome AF: 0.000599

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000360

Gnomad OTH exome AF: 0.00149

GnomAD4 exome AF: 0.00120 AC: 1750 AN: 1456126 Hom.: 35 Cov.: 33 AF XY: 0.00102 AC XY: 738 AN XY: 724624

African (AFR) AF: 0.0391 AC: 1299 AN: 33182

American (AMR) AF: 0.00239 AC: 107 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.000307 AC: 8 AN: 26090

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39628

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86054

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53036

Middle Eastern (MID) AF: 0.00291 AC: 14 AN: 4818

European-Non Finnish (NFE) AF: 0.000168 AC: 186 AN: 1108578

Other (OTH) AF: 0.00208 AC: 125 AN: 60052

GnomAD4 genome AF: 0.0102 AC: 1541 AN: 151474 Hom.: 25 Cov.: 32 AF XY: 0.00959 AC XY: 710 AN XY: 74056

African (AFR) AF: 0.0358 AC: 1463 AN: 40816

American (AMR) AF: 0.00328 AC: 50 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 67992

Other (OTH) AF: 0.00333 AC: 7 AN: 2104

Alfa AF: 0.0154 Hom.: 12

Bravo AF: 0.0114

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.2
DANN	Benign	0.88
PhyloP100		0.055
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs201470386; hg19: chr17-4805188;