Genetic Variant EMICERI:n.5741C>T (chr9-27541043-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000645861.1(EMICERI):n.5741C>T 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 0.396 in 152,072 control chromosomes in the GnomAD database, including 14,146 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 0.40 ( 14143 hom., cov: 32)

Exomes 𝑓: 0.42 ( 3 hom. )

Consequence

EMICERI
ENST00000645861.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0280

Publications

12 publications found

Variant links:

Genes affected

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

EMICERI links:

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

C9orf72 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EMICERI	ENST00000645861.1 link	n.5741C>T		non_coding_transcript_exon_variant	Exon 2 of 2
C9orf72	ENST00000673600.1 link	n.*268-4757G>A		intron_variant	Intron 11 of 11			ENSP00000500650.1		A0A5F9ZHW7

Frequencies

GnomAD3 genomes

AF:

0.397

AC:

60280

AN:

151916

Hom.:

14145

Cov.:

show subpopulations

Gnomad AFR

AF:

0.135

Gnomad AMI

AF:

0.468

Gnomad AMR

AF:

0.471

Gnomad ASJ

AF:

0.625

Gnomad EAS

AF:

0.594

Gnomad SAS

AF:

0.483

Gnomad FIN

AF:

0.509

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.487

Gnomad OTH

AF:

0.423

GnomAD4 exome

AF:

0.421

AC:

AN:

Hom.:

Cov.:

AF XY:

0.409

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.545

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.396

AC:

60269

AN:

152034

Hom.:

14143

Cov.:

AF XY:

0.402

AC XY:

29879

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.134

AC:

5577

AN:

41492

American (AMR)

AF:

0.471

AC:

7197

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.625

AC:

2169

AN:

3470

East Asian (EAS)

AF:

0.594

AC:

3062

AN:

5158

South Asian (SAS)

AF:

0.483

AC:

2333

AN:

4830

European-Finnish (FIN)

AF:

0.509

AC:

5361

AN:

10540

Middle Eastern (MID)

AF:

0.463

AC:

136

AN:

294

European-Non Finnish (NFE)

AF:

0.488

AC:

33123

AN:

67944

Other (OTH)

AF:

0.419

AC:

884

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1667

3334

5001

6668

8335

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

572

1144

1716

2288

2860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.442

Hom.:

5240

Bravo

AF:

0.381

Asia WGS

AF:

0.465

AC:

1617

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

6.5

(source)

DANN

Benign

0.75

PhyloP100

-0.028

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over