rs1869485

Positions:

• chr15-60454406-G-A

Variant summary

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

The NM_024611.6(ICE2):​c.943+597C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 151,892 control chromosomes in the GnomAD database, including 22,572 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 0.52 (22572 hom., cov: 32)
• Consequence: ICE2 NM_024611.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.740

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ICE2	NM_024611.6	c.943+597C>T		intron_variant		ENST00000261520.9	NP_078887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ICE2	ENST00000261520.9	c.943+597C>T		intron_variant		1	NM_024611.6	ENSP00000261520	P1
ICE2	ENST00000558512.5	c.943+597C>T		intron_variant		1		ENSP00000452714
ICE2	ENST00000561114.5	c.943+597C>T		intron_variant		1		ENSP00000454162
ICE2	ENST00000558181.5	c.*561+597C>T		intron_variant, NMD_transcript_variant		1		ENSP00000453593

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79104 AN: 151774 Hom.: 22550 Cov.: 32

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.707

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.836

Gnomad SAS AF: 0.781

Gnomad FIN AF: 0.714

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.521 AC: 79150 AN: 151892 Hom.: 22572 Cov.: 32 AF XY: 0.534 AC XY: 39653 AN XY: 74246

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.597

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.836

Gnomad4 SAS AF: 0.781

Gnomad4 FIN AF: 0.714

Gnomad4 NFE AF: 0.572

Gnomad4 OTH AF: 0.508

Alfa AF: 0.569 Hom.: 11570

Bravo AF: 0.498

Asia WGS AF: 0.780 AC: 2709 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.1
DANN	Benign	0.57

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: rs1869485; hg19: chr15-60746605;