5-5449254-C-T

Variant names:

• chr5-5449254-C-T
• rs2578553
• NM_015325.3:c.604+1357C>T

Variant summary

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

The NM_015325.3(ICE1):​c.604+1357C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 151,838 control chromosomes in the GnomAD database, including 16,116 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 0.45 (16116 hom., cov: 32)
• Consequence: ICE1 NM_015325.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015325.3. 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
	ICE1	NM_015325.3	MANE Select	c.604+1357C>T		intron	N/A	NP_056140.1	Q9Y2F5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ICE1	ENST00000296564.9	TSL:1 MANE Select	c.604+1357C>T		intron	N/A	ENSP00000296564.7	Q9Y2F5
	ICE1	ENST00000512608.5	TSL:4	c.373+1357C>T		intron	N/A	ENSP00000485617.1	A0A096LPH9

Frequencies

GnomAD3 genomes AF: 0.448 AC: 67918 AN: 151720 Hom.: 16074 Cov.: 32

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.448 AC: 68023 AN: 151838 Hom.: 16116 Cov.: 32 AF XY: 0.450 AC XY: 33404 AN XY: 74178

African (AFR) AF: 0.598 AC: 24742 AN: 41396

American (AMR) AF: 0.426 AC: 6493 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1181 AN: 3472

East Asian (EAS) AF: 0.627 AC: 3234 AN: 5156

South Asian (SAS) AF: 0.353 AC: 1699 AN: 4816

European-Finnish (FIN) AF: 0.452 AC: 4744 AN: 10496

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.364 AC: 24724 AN: 67940

Other (OTH) AF: 0.398 AC: 839 AN: 2106

Alfa AF: 0.386 Hom.: 41888

Bravo AF: 0.452

Asia WGS AF: 0.492 AC: 1708 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.5
DANN	Benign	0.18
PhyloP100		-0.028
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: rs2578553; hg19: chr5-5449367; COSMIC: COSV56827248;