rs3861016

chr9-27543043-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000645861.1(EMICERI):n.7741T>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 0.0639 in 152,308 control chromosomes in the GnomAD database, including 461 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 0.064 (461 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: EMICERI ENST00000645861.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.680

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EMICERI	ENST00000645861.1	n.7741T>G		non_coding_transcript_exon_variant	2/2
C9orf72	ENST00000673600.1	c.*267+5072A>C		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0639 AC: 9728 AN: 152190 Hom.: 460 Cov.: 33

Gnomad AFR AF: 0.0144

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0707

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0666

Gnomad OTH AF: 0.0756

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

GnomAD4 genome AF: 0.0639 AC: 9726 AN: 152308 Hom.: 461 Cov.: 33 AF XY: 0.0674 AC XY: 5023 AN XY: 74478

Gnomad4 AFR AF: 0.0144

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.0707

Gnomad4 NFE AF: 0.0666

Gnomad4 OTH AF: 0.0748

Alfa AF: 0.0628 Hom.: 50

Bravo AF: 0.0648

Asia WGS AF: 0.129 AC: 448 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	6.0
Dann	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3861016; hg19: chr9-27543041;