dbSNP rs12907068: ICE2:c.409-99T>C (chr15-60466812-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_024611.6(ICE2):c.409-99T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 976,488 control chromosomes in the GnomAD database, including 8,097 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 0.095 ( 903 hom., cov: 33)

Exomes 𝑓: 0.12 ( 7194 hom. )

Consequence

ICE2
NM_024611.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.567

Publications

2 publications found

Variant links:

Genes affected

ICE2 (HGNC:29885): (interactor of little elongation complex ELL subunit 2) This gene encodes a protein component of the little elongation complex (LEC), which plays a role in small nuclear RNA (snRNA) transcription. The LEC regulates snRNA transcription by enhancing both RNA Polymerase II occupancy and transcriptional elongation. The encoded protein and other LEC components have been shown to localize to Cajal bodies, which are sites of ribonucleoprotein (RNP) complex assembly. Pseudogenes of this gene have been identified on chromosomes 3 and 4. [provided by RefSeq, May 2017]

ICE2 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=-0.79).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024611.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ICE2	NM_024611.6	MANE Select	c.409-99T>C	intron	N/A	NP_078887.2
ICE2	NM_001018089.3		c.-3-99T>C	intron	N/A	NP_001018099.1
ICE2	NM_001276385.2		c.409-99T>C	intron	N/A	NP_001263314.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ICE2	ENST00000261520.9	TSL:1 MANE Select	c.409-99T>C	intron	N/A	ENSP00000261520.4
ICE2	ENST00000561114.5	TSL:1	c.409-99T>C	intron	N/A	ENSP00000454162.1
ICE2	ENST00000558512.5	TSL:1	c.409-99T>C	intron	N/A	ENSP00000452714.1

Frequencies

GnomAD3 genomes

AF:

0.0956

AC:

14548

AN:

152160

Hom.:

903

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0264

Gnomad AMI

AF:

0.0713

Gnomad AMR

AF:

0.0919

Gnomad ASJ

AF:

0.195

Gnomad EAS

AF:

0.0953

Gnomad SAS

AF:

0.0478

Gnomad FIN

AF:

0.0882

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.137

Gnomad OTH

AF:

0.123

GnomAD4 exome

AF:

0.125

AC:

103000

AN:

824212

Hom.:

7194

AF XY:

0.123

AC XY:

51605

AN XY:

420306

show subpopulations

African (AFR)

AF:

0.0246

AC:

479

AN:

19498

American (AMR)

AF:

0.0724

AC:

1629

AN:

22510

Ashkenazi Jewish (ASJ)

AF:

0.190

AC:

3258

AN:

17156

East Asian (EAS)

AF:

0.0854

AC:

2984

AN:

34926

South Asian (SAS)

AF:

0.0504

AC:

2832

AN:

56222

European-Finnish (FIN)

AF:

0.0972

AC:

3233

AN:

33252

Middle Eastern (MID)

AF:

0.229

AC:

796

AN:

3478

European-Non Finnish (NFE)

AF:

0.139

AC:

83017

AN:

599000

Other (OTH)

AF:

0.125

AC:

4772

AN:

38170

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

4259

8517

12776

17034

21293

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2320

4640

6960

9280

11600

<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:

0.0954

AC:

14534

AN:

152276

Hom.:

903

Cov.:

AF XY:

0.0928

AC XY:

6914

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0263

AC:

1093

AN:

41568

American (AMR)

AF:

0.0917

AC:

1402

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.195

AC:

677

AN:

3466

East Asian (EAS)

AF:

0.0951

AC:

494

AN:

5192

South Asian (SAS)

AF:

0.0480

AC:

232

AN:

4830

European-Finnish (FIN)

AF:

0.0882

AC:

936

AN:

10608

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.137

AC:

9317

AN:

68000

Other (OTH)

AF:

0.121

AC:

256

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

662

1325

1987

2650

3312

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

162

324

486

648

810

<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:

0.124

Hom.:

582

Bravo

AF:

0.0960

Asia WGS

AF:

0.0510

AC:

178

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.5

(source)

DANN

Benign

0.79

PhyloP100

0.57

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over