rs11071537

chr15-60471877-A-Gchr15-60471877-A-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.85).
• 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/exons	MANE	UniProt
ICE2	NM_024611.6	c.147-3555T>C		intron_variant		ENST00000261520.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ICE2	ENST00000261520.9	c.147-3555T>C		intron_variant		1	NM_024611.6	P1

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

Gnomad4 AFR AF: 0.528

Gnomad4 AMR AF: 0.714

Gnomad4 ASJ AF: 0.689

Gnomad4 EAS AF: 0.935

Gnomad4 SAS AF: 0.830

Gnomad4 FIN AF: 0.808

Gnomad4 NFE AF: 0.711

Gnomad4 OTH AF: 0.673

Alfa AF: 0.704 Hom.: 38582

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

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: rs11071537; hg19: chr15-60764076;