rs1869485

Variant names:

• chr15-60454406-G-A
• rs1869485
• NM_024611.6:c.943+597C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ICE2	NM_024611.6	MANE Select	c.943+597C>T		intron	N/A	NP_078887.2
	ICE2	NM_001018089.3		c.532+597C>T		intron	N/A	NP_001018099.1
	ICE2	NM_001276385.2		c.943+597C>T		intron	N/A	NP_001263314.1	H0YNU9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ICE2	ENST00000261520.9	TSL:1 MANE Select	c.943+597C>T		intron	N/A	ENSP00000261520.4	Q659A1-1
	ICE2	ENST00000561114.5	TSL:1	c.943+597C>T		intron	N/A	ENSP00000454162.1	H0YNU9
	ICE2	ENST00000558512.5	TSL:1	c.943+597C>T		intron	N/A	ENSP00000452714.1	H0YK97

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

African (AFR) AF: 0.291 AC: 12057 AN: 41410

American (AMR) AF: 0.597 AC: 9119 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1722 AN: 3464

East Asian (EAS) AF: 0.836 AC: 4330 AN: 5182

South Asian (SAS) AF: 0.781 AC: 3756 AN: 4810

European-Finnish (FIN) AF: 0.714 AC: 7533 AN: 10552

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.572 AC: 38826 AN: 67898

Other (OTH) AF: 0.508 AC: 1068 AN: 2102

Alfa AF: 0.568 Hom.: 12784

Bravo AF: 0.498

Asia WGS AF: 0.780 AC: 2709 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.1
DANN	Benign	0.57
PhyloP100		0.74
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1869485; hg19: chr15-60746605;