12-92422628-G-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The ENST00000752702.1(CLLU1-AS1):​n.152-3C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLLU1-AS1 ENST00000752702.1 splice_region, 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: BayesDel_addAF computational evidence supports a deleterious effect, 0.255

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000752702.1. 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>T		non_coding_transcript_exon	Exon 2 of 4
	CLLU1	NR_027932.1		n.305+793G>A		intron	N/A
	CLLU1	NR_027933.1		n.305+793G>A		intron	N/A

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.13
CADD	Benign	11
DANN	Uncertain	1.0
Eigen	Benign	0.16
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.013	N
PhyloP100		-0.0080
Vest4		0.025
GERP RS		0.99

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.22		Position offset: 8

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

Other links and lift over

dbSNP: rs1004525017; hg19: chr12-92816404;