12-92422628-G-C

Position:

• chr12-92422628-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000646751.1(CLLU1-AS1):​n.63C>G variant causes a non coding transcript exon 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLLU1-AS1 ENST00000646751.1 non_coding_transcript_exon
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00800

Genes affected

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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.084570795).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLLU1	NR_027932.1	n.305+793G>C		intron_variant, non_coding_transcript_variant
CLLU1-AS1	NR_144319.2	n.91-1455C>G		intron_variant, non_coding_transcript_variant
CLLU1-AS1	NR_164161.1	n.63C>G		non_coding_transcript_exon_variant	2/4
CLLU1	NR_027933.1	n.305+793G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLLU1-AS1	ENST00000646751.1	n.63C>G		non_coding_transcript_exon_variant	2/4
CLLU1	ENST00000472839.6	n.305+793G>C		intron_variant, non_coding_transcript_variant		1
CLLU1	ENST00000512817.1	n.305+793G>C		intron_variant, non_coding_transcript_variant		1
CLLU1	ENST00000589406.1	n.1098G>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2021

The c.61C>G (p.Q21E) alteration is located in exon 2 (coding exon 2) of the CLLU1OS gene. This alteration results from a C to G substitution at nucleotide position 61, causing the glutamine (Q) at amino acid position 21 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	8.7
DANN	Benign	0.84
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.00085	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.024
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.10	B
Vest4		0.27
MutPred		0.19		Gain of catalytic residue at P25 (P = 0.0099);
MVP		0.014
MPC		0.21
ClinPred		0.13	T
GERP RS		0.99
Varity_R		0.27
gMVP		0.0043

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-92816404;