NM_024611.6:c.147-3555T>C

Variant names:

• chr15-60471877-A-G
• rs11071537
• NM_024611.6:c.147-3555T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024611.6(ICE2):​c.147-3555T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 151,720 control chromosomes in the GnomAD database, including 35,846 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 0.68 (35846 hom., cov: 30)
• Consequence: ICE2 NM_024611.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0930
• Publications: 9 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ICE2	NM_024611.6	c.147-3555T>C		intron_variant	Intron 3 of 15	ENST00000261520.9	NP_078887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ICE2	ENST00000261520.9	c.147-3555T>C		intron_variant	Intron 3 of 15	1	NM_024611.6	ENSP00000261520.4

Frequencies

GnomAD3 genomes AF: 0.678 AC: 102852 AN: 151602 Hom.: 35814 Cov.: 30

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.936

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.670

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

GnomAD4 genome AF: 0.678 AC: 102935 AN: 151720 Hom.: 35846 Cov.: 30 AF XY: 0.687 AC XY: 50939 AN XY: 74144

African (AFR) AF: 0.528 AC: 21820 AN: 41356

American (AMR) AF: 0.714 AC: 10897 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 2390 AN: 3470

East Asian (EAS) AF: 0.935 AC: 4833 AN: 5168

South Asian (SAS) AF: 0.830 AC: 3993 AN: 4812

European-Finnish (FIN) AF: 0.808 AC: 8446 AN: 10454

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.711 AC: 48261 AN: 67886

Other (OTH) AF: 0.673 AC: 1425 AN: 2116

Alfa AF: 0.701 Hom.: 44711

Bravo AF: 0.665

Asia WGS AF: 0.860 AC: 2984 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.4
DANN	Benign	0.44
PhyloP100		-0.093
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: rs11071537; hg19: chr15-60764076;