rs17769217

Variant names:

• chr9-27543533-C-G
• rs17769217
• ENST00000645861.1:n.8231C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-27543533-C-G
• chr9-27543533-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000645861.1(EMICERI):​n.8231C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 132,914 control chromosomes in the GnomAD database, including 883 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (883 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EMICERI ENST00000645861.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.24
• Publications: 3 publications found

Genes affected

EMICERI (HGNC:53656): (EQTN MOB3B IFNK C9orf72 enhancer RNA I)

C9orf72 (HGNC:28337): (C9orf72-SMCR8 complex subunit) The protein encoded by this gene plays an important role in the regulation of endosomal trafficking, and has been shown to interact with Rab proteins that are involved in autophagy and endocytic transport. Expansion of a GGGGCC repeat from 2-22 copies to 700-1600 copies in the intronic sequence between alternate 5' exons in transcripts from this gene is associated with 9p-linked ALS (amyotrophic lateral sclerosis) and FTD (frontotemporal dementia) (PMID: 21944778, 21944779). Studies suggest that hexanucleotide expansions could result in the selective stabilization of repeat-containing pre-mRNA, and the accumulation of insoluble dipeptide repeat protein aggregates that could be pathogenic in FTD-ALS patients (PMID: 23393093). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2016]

C9orf72 Gene-Disease associations (from GenCC):

• frontotemporal dementia and/or amyotrophic lateral sclerosis 1

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
• progressive myoclonus epilepsy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000645861.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMICERI	ENST00000645861.1		n.8231C>G		non_coding_transcript_exon	Exon 2 of 2
	C9orf72	ENST00000673600.1		n.*267+4582G>C		intron	N/A	ENSP00000500650.1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 14608 AN: 132820 Hom.: 883 Cov.: 33

Gnomad AFR AF: 0.0444

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.0998

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.000990

Gnomad SAS AF: 0.0910

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.113

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.120

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.110 AC: 14606 AN: 132914 Hom.: 883 Cov.: 33 AF XY: 0.113 AC XY: 7222 AN XY: 64104

African (AFR) AF: 0.0444 AC: 1534 AN: 34568

American (AMR) AF: 0.0996 AC: 1223 AN: 12278

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 335 AN: 3230

East Asian (EAS) AF: 0.000744 AC: 3 AN: 4032

South Asian (SAS) AF: 0.0909 AC: 326 AN: 3588

European-Finnish (FIN) AF: 0.217 AC: 1945 AN: 8982

Middle Eastern (MID) AF: 0.112 AC: 31 AN: 278

European-Non Finnish (NFE) AF: 0.139 AC: 8828 AN: 63342

Other (OTH) AF: 0.119 AC: 209 AN: 1758

Alfa AF: 0.0565 Hom.: 57

Bravo AF: 0.0872

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.5
DANN	Benign	0.69
PhyloP100		-2.2

Splicing

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

Other links and lift over

dbSNP: rs17769217; hg19: chr9-27543531;