rs2578553

Positions:

• chr5-5449254-C-A
• chr5-5449254-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015325.3(ICE1):​c.604+1357C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: ICE1 NM_015325.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280

Genes affected

ICE1 (HGNC:29154): (interactor of little elongation complex ELL subunit 1) Enables protein-macromolecule adaptor activity. Involved in several processes, including positive regulation of intracellular protein transport; positive regulation of transcription by RNA polymerase III; and snRNA transcription. Located in Cajal body; histone locus body; and transcriptionally active chromatin. Part of transcription elongation factor complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ICE1	NM_015325.3	c.604+1357C>A		intron_variant		ENST00000296564.9	NP_056140.1
ICE1	XM_011513999.3	c.604+1357C>A		intron_variant			XP_011512301.1
ICE1	XM_047417046.1	c.604+1357C>A		intron_variant			XP_047273002.1
ICE1	XM_047417047.1	c.604+1357C>A		intron_variant			XP_047273003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ICE1	ENST00000296564.9	c.604+1357C>A		intron_variant		1	NM_015325.3	ENSP00000296564	P1
ICE1	ENST00000512608.5	c.373+1357C>A		intron_variant		4		ENSP00000485617

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.26

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: rs2578553; hg19: chr5-5449367;