rs77481135

Variant names:

• chr17-4903071-C-T
• rs77481135
• NM_000080.4:c.-8G>A

Variant summary

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

The NM_000080.4(CHRNE):​c.-8G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00642 in 1,613,906 control chromosomes in the GnomAD database, including 552 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (285 hom., cov: 31)
  • Exomes 𝑓: 0.0036 (267 hom.)
• Consequence: CHRNE NM_000080.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.514
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 17-4903071-C-T is Benign according to our data. Variant chr17-4903071-C-T is described in ClinVar as Benign. ClinVar VariationId is 254888.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNE	NM_000080.4	MANE Select	c.-8G>A		5_prime_UTR	Exon 1 of 12	NP_000071.1
	C17orf107	NM_001145536.2	MANE Select	c.*2538C>T		downstream_gene	N/A	NP_001139008.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNE	ENST00000649488.2	MANE Select	c.-8G>A		5_prime_UTR	Exon 1 of 12	ENSP00000497829.1
	CHRNE	ENST00000649830.1		c.-887-308G>A		intron	N/A	ENSP00000496907.1
	C17orf107	ENST00000381365.4	TSL:2 MANE Select	c.*2538C>T		downstream_gene	N/A	ENSP00000370770.3

Frequencies

GnomAD3 genomes AF: 0.0329 AC: 5006 AN: 151954 Hom.: 279 Cov.: 31

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000831

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000559

Gnomad OTH AF: 0.0211

GnomAD2 exomes AF: 0.00943 AC: 2370 AN: 251254 AF XY: 0.00694

Gnomad AFR exome AF: 0.117

Gnomad AMR exome AF: 0.0105

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000449

Gnomad OTH exome AF: 0.00734

GnomAD4 exome AF: 0.00364 AC: 5321 AN: 1461834 Hom.: 267 Cov.: 32 AF XY: 0.00318 AC XY: 2315 AN XY: 727230

African (AFR) AF: 0.117 AC: 3900 AN: 33476

American (AMR) AF: 0.0110 AC: 491 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000383 AC: 33 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00867 AC: 50 AN: 5768

European-Non Finnish (NFE) AF: 0.000246 AC: 274 AN: 1111992

Other (OTH) AF: 0.00947 AC: 572 AN: 60394

GnomAD4 genome AF: 0.0331 AC: 5034 AN: 152072 Hom.: 285 Cov.: 31 AF XY: 0.0314 AC XY: 2335 AN XY: 74338

African (AFR) AF: 0.114 AC: 4705 AN: 41436

American (AMR) AF: 0.0156 AC: 239 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000559 AC: 38 AN: 68006

Other (OTH) AF: 0.0209 AC: 44 AN: 2106

Alfa AF: 0.0159 Hom.: 79

Bravo AF: 0.0387

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Congenital myasthenic syndrome (2)
-	-	2	not specified (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	13
DANN	Benign	0.73
PhyloP100		0.51
PromoterAI		-0.0091	Neutral
Mutation Taster		=300/0	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: rs77481135; hg19: chr17-4806366;