5-5461120-A-G

Variant names:

• chr5-5461120-A-G
• rs10475299
• NM_015325.3:c.1786A>G

Variant summary

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

The NM_015325.3(ICE1):​c.1786A>G​(p.Lys596Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 1,613,960 control chromosomes in the GnomAD database, including 1,945 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.063 (997 hom., cov: 33)
  • Exomes 𝑓: 0.0064 (948 hom.)
• Consequence: ICE1 NM_015325.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.206
• Publications: 9 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 (MetaRNN=0.0038980544).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.217 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ICE1	NM_015325.3	MANE Select	c.1786A>G	p.Lys596Glu	missense	Exon 13 of 19	NP_056140.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ICE1	ENST00000296564.9	TSL:1 MANE Select	c.1786A>G	p.Lys596Glu	missense	Exon 13 of 19	ENSP00000296564.7

Frequencies

GnomAD3 genomes AF: 0.0631 AC: 9606 AN: 152144 Hom.: 996 Cov.: 33

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0207

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000735

Gnomad OTH AF: 0.0421

GnomAD2 exomes AF: 0.0157 AC: 3909 AN: 249014 AF XY: 0.0122

Gnomad AFR exome AF: 0.227

Gnomad AMR exome AF: 0.00886

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000541

Gnomad OTH exome AF: 0.00497

GnomAD4 exome AF: 0.00638 AC: 9326 AN: 1461698 Hom.: 948 Cov.: 39 AF XY: 0.00553 AC XY: 4018 AN XY: 727128

African (AFR) AF: 0.229 AC: 7659 AN: 33476

American (AMR) AF: 0.0102 AC: 458 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000765 AC: 66 AN: 86258

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53398

Middle Eastern (MID) AF: 0.00641 AC: 37 AN: 5768

European-Non Finnish (NFE) AF: 0.000262 AC: 291 AN: 1111866

Other (OTH) AF: 0.0134 AC: 812 AN: 60374

GnomAD4 genome AF: 0.0633 AC: 9634 AN: 152262 Hom.: 997 Cov.: 33 AF XY: 0.0604 AC XY: 4494 AN XY: 74450

African (AFR) AF: 0.221 AC: 9176 AN: 41500

American (AMR) AF: 0.0206 AC: 316 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000735 AC: 50 AN: 68022

Other (OTH) AF: 0.0416 AC: 88 AN: 2114

Alfa AF: 0.0239 Hom.: 689

Bravo AF: 0.0721

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.221 AC: 821

ESP6500EA AF: 0.000610 AC: 5

ExAC AF: 0.0195 AC: 2357

Asia WGS AF: 0.00866 AC: 30 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000948

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	2.4
DANN	Benign	0.90
DEOGEN2	Benign	0.020	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.21
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.020
Sift	Benign	0.30	T
Sift4G	Benign	0.66	T
Polyphen		0.0090	B
Vest4		0.035
MPC		0.15
ClinPred		0.0018	T
GERP RS		0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.042
gMVP		0.080
Mutation Taster		=98/2	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: rs10475299; hg19: chr5-5461233; COSMIC: COSV56825989;