15-60448642-C-T

Variant names:

• chr15-60448642-C-T
• rs17270146
• NM_024611.6:c.2119+206G>A

Variant summary

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

The NM_024611.6(ICE2):​c.2119+206G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,072 control chromosomes in the GnomAD database, including 4,931 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 0.25 (4931 hom., cov: 33)
• Consequence: ICE2 NM_024611.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.620

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ICE2	NM_024611.6	c.2119+206G>A		intron_variant	Intron 10 of 15	ENST00000261520.9	NP_078887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ICE2	ENST00000261520.9	c.2119+206G>A		intron_variant	Intron 10 of 15	1	NM_024611.6	ENSP00000261520.4
ICE2	ENST00000558181.5	n.*1737+206G>A		intron_variant	Intron 10 of 15	1		ENSP00000453593.1
ICE2	ENST00000561328.1	n.1175+206G>A		intron_variant	Intron 2 of 2	1
ICE2	ENST00000561144.1	n.104+206G>A		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37353 AN: 151954 Hom.: 4934 Cov.: 33

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.0667

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.275

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.246 AC: 37360 AN: 152072 Hom.: 4931 Cov.: 33 AF XY: 0.241 AC XY: 17879 AN XY: 74338

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.260

Gnomad4 ASJ AF: 0.300

Gnomad4 EAS AF: 0.0673

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.273

Alfa AF: 0.283 Hom.: 12459

Bravo AF: 0.249

Asia WGS AF: 0.125 AC: 436 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.56
DANN	Benign	0.56

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: rs17270146; hg19: chr15-60740841;