ENST00000472839.6:n.305+793G>T

Variant names:

• chr12-92422628-G-T
• rs1004525017
• ENST00000472839.6:n.305+793G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000472839.6(CLLU1):​n.305+793G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,398 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CLLU1 ENST00000472839.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800
• Publications: 0 publications found

Genes affected

CLLU1 (HGNC:29841): (chronic lymphocytic leukemia up-regulated 1) Expression of this gene has been shown to be upregulated in some individuals with chronic lymphocytic leukemia (CLL), and has been used for prognostic and diagnostic purposes. This gene was originally identified as a human-specific putative protein-coding gene due to the presence of a peptide (PAp00140670, HIIYSTFLSK) that could have supported translation at this locus. This peptide is not present in more recent builds of PeptideAtlas, and the presence of a protein product at this locus has not been independently verified. For this reason, this gene is being represented as non-coding. Sequence comparisons to other primates indicates that no other primate is predicted to contain an open reading frame. [provided by RefSeq, Feb 2017]

CLLU1-AS1 (HGNC:24070): (CLLU1 antisense RNA 1)

ENSG00000266923 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09544629).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000472839.6. 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
	CLLU1-AS1	NR_164161.1		n.63C>A		non_coding_transcript_exon	Exon 2 of 4
	CLLU1	NR_027932.1		n.305+793G>T		intron	N/A
	CLLU1	NR_027933.1		n.305+793G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLLU1	ENST00000472839.6	TSL:1	n.305+793G>T		intron	N/A
	CLLU1	ENST00000512817.1	TSL:1	n.305+793G>T		intron	N/A
	CLLU1	ENST00000589406.1	TSL:6	n.1098G>T		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451398 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 721496

African (AFR) AF: 0.00 AC: 0 AN: 33164

American (AMR) AF: 0.00 AC: 0 AN: 43432

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25910

East Asian (EAS) AF: 0.00 AC: 0 AN: 39378

South Asian (SAS) AF: 0.00 AC: 0 AN: 85052

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52904

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 9.04e-7 AC: 1 AN: 1105928

Other (OTH) AF: 0.00 AC: 0 AN: 59882

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	8.1
DANN	Benign	0.85
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.00097	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.0080
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.019
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.21	B
Vest4		0.27
MutPred		0.23		Gain of catalytic residue at P25 (P = 0.0099)
MVP		0.014
MPC		0.25
ClinPred		0.13	T
GERP RS		0.99
Varity_R		0.32
gMVP		0.012

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: rs1004525017; hg19: chr12-92816404;