17-4899175-CGGGCCA-C

Variant names:

• chr17-4899175-CGGGCCA-C
• rs148340961
• NM_000080.4:c.1219+17_1219+22delTGGCCC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000080.4(CHRNE):​c.1219+17_1219+22delTGGCCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0817 in 1,594,800 control chromosomes in the GnomAD database, including 5,697 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.071 (434 hom., cov: 31)
  • Exomes 𝑓: 0.083 (5263 hom.)
• Consequence: CHRNE NM_000080.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.355
• Publications: 0 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 -16 ACMG points.

• BP6: Variant 17-4899175-CGGGCCA-C is Benign according to our data. Variant chr17-4899175-CGGGCCA-C is described in ClinVar as Benign. ClinVar VariationId is 254890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0894 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000080.4. 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
	CHRNE	NM_000080.4	MANE Select	c.1219+17_1219+22delTGGCCC		intron	N/A	NP_000071.1	Q04844

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNE	ENST00000649488.2	MANE Select	c.1219+17_1219+22delTGGCCC		intron	N/A	ENSP00000497829.1	Q04844
	CHRNE	ENST00000649830.1		c.286+17_286+22delTGGCCC		intron	N/A	ENSP00000496907.1	A0A3B3IRM1
	CHRNE	ENST00000572438.1	TSL:5	n.905+17_905+22delTGGCCC		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0715 AC: 10871 AN: 152056 Hom.: 433 Cov.: 31

Gnomad AFR AF: 0.0321

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.0595

Gnomad ASJ AF: 0.0648

Gnomad EAS AF: 0.0482

Gnomad SAS AF: 0.0356

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0913

Gnomad OTH AF: 0.0564

GnomAD2 exomes AF: 0.0690 AC: 14452 AN: 209320 AF XY: 0.0692

Gnomad AFR exome AF: 0.0268

Gnomad AMR exome AF: 0.0457

Gnomad ASJ exome AF: 0.0583

Gnomad EAS exome AF: 0.0405

Gnomad FIN exome AF: 0.130

Gnomad NFE exome AF: 0.0901

Gnomad OTH exome AF: 0.0766

GnomAD4 exome AF: 0.0828 AC: 119405 AN: 1442626 Hom.: 5263 AF XY: 0.0814 AC XY: 58365 AN XY: 716716

African (AFR) AF: 0.0285 AC: 940 AN: 33010

American (AMR) AF: 0.0468 AC: 2011 AN: 42992

Ashkenazi Jewish (ASJ) AF: 0.0594 AC: 1536 AN: 25842

East Asian (EAS) AF: 0.0704 AC: 2713 AN: 38558

South Asian (SAS) AF: 0.0289 AC: 2434 AN: 84142

European-Finnish (FIN) AF: 0.133 AC: 6297 AN: 47280

Middle Eastern (MID) AF: 0.0570 AC: 326 AN: 5720

European-Non Finnish (NFE) AF: 0.0894 AC: 98796 AN: 1105418

Other (OTH) AF: 0.0729 AC: 4352 AN: 59664

GnomAD4 genome AF: 0.0714 AC: 10872 AN: 152174 Hom.: 434 Cov.: 31 AF XY: 0.0732 AC XY: 5443 AN XY: 74398

African (AFR) AF: 0.0321 AC: 1335 AN: 41544

American (AMR) AF: 0.0594 AC: 909 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0648 AC: 225 AN: 3472

East Asian (EAS) AF: 0.0483 AC: 249 AN: 5150

South Asian (SAS) AF: 0.0356 AC: 172 AN: 4826

European-Finnish (FIN) AF: 0.144 AC: 1531 AN: 10604

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0913 AC: 6206 AN: 67954

Other (OTH) AF: 0.0553 AC: 117 AN: 2116

Alfa AF: 0.0790 Hom.: 84

Bravo AF: 0.0615

Asia WGS AF: 0.0390 AC: 136 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.35
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs148340961; hg19: chr17-4802470;