rs111413308

chr17-4901883-G-Achr17-4901883-G-C

Variant summary

Our verdict is Benign. Variant got -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:2
• Conservation: PhyloP100: 0.579

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C17orf107	NM_001145536.2	c.*1350G>A		3_prime_UTR_variant	3/3	ENST00000381365.4
CHRNE	NM_000080.4	c.500+49C>T		intron_variant		ENST00000649488.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C17orf107	ENST00000381365.4	c.*1350G>A		3_prime_UTR_variant	3/3	2	NM_001145536.2	A2
CHRNE	ENST00000649488.2	c.500+49C>T		intron_variant			NM_000080.4	P1
CHRNE	ENST00000649830.1	c.-434+49C>T		intron_variant
CHRNE	ENST00000575637.1	n.274+96C>T		intron_variant, non_coding_transcript_variant		3

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

GnomAD3 exomes AF: 0.00890 AC: 2161 AN: 242944 Hom.: 97 AF XY: 0.00674 AC XY: 894 AN XY: 132684

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 SAS exome AF: 0.000295

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

Gnomad4 AFR exome AF: 0.0902

Gnomad4 AMR exome AF: 0.00959

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000397

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000268

Gnomad4 OTH exome AF: 0.00830

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

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.0158

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000642

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000573

Gnomad4 OTH AF: 0.0223

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.6
Dann	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs111413308; hg19: chr17-4805178;