5-5449254-C-T

Position:

• chr5-5449254-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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.

Transcripts

RefSeq

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

Ensembl

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

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

Gnomad4 AFR AF: 0.598

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.627

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.398

Alfa AF: 0.370 Hom.: 16608

Bravo AF: 0.452

Asia WGS AF: 0.492 AC: 1708 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.5
DANN	Benign	0.18

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; COSMIC: COSV56827248;