rs12907068

Positions:

• chr15-60466812-A-G

Variant summary

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

The ENST00000261520.9(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 ENST00000261520.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.567

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ICE2	NM_024611.6	c.409-99T>C		intron_variant		ENST00000261520.9	NP_078887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ICE2	ENST00000261520.9	c.409-99T>C		intron_variant		1	NM_024611.6	ENSP00000261520	P1

Frequencies

GnomAD3 genomes AF: 0.0956 AC: 14548 AN: 152160 Hom.: 903 Cov.: 33

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

Gnomad4 AFR exome AF: 0.0246

Gnomad4 AMR exome AF: 0.0724

Gnomad4 ASJ exome AF: 0.190

Gnomad4 EAS exome AF: 0.0854

Gnomad4 SAS exome AF: 0.0504

Gnomad4 FIN exome AF: 0.0972

Gnomad4 NFE exome AF: 0.139

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.0954 AC: 14534 AN: 152276 Hom.: 903 Cov.: 33 AF XY: 0.0928 AC XY: 6914 AN XY: 74478

Gnomad4 AFR AF: 0.0263

Gnomad4 AMR AF: 0.0917

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.0951

Gnomad4 SAS AF: 0.0480

Gnomad4 FIN AF: 0.0882

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.121

Alfa AF: 0.123 Hom.: 505

Bravo AF: 0.0960

Asia WGS AF: 0.0510 AC: 178 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.5
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: rs12907068; hg19: chr15-60759011;