12-92422565-G-C

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NR_164161.1(CLLU1-AS1):n.126C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000477 in 1,613,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

CLLU1-AS1
NR_164161.1 non_coding_transcript_exon

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.251

Variant links:

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 links:

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

CLLU1-AS1 links:

ENSG00000266923 (HGNC:):

ENSG00000266923 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.014653802).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
CLLU1-AS1	NR_164161.1 link	n.126C>G	non_coding_transcript_exon_variant	Exon 2 of 4
CLLU1	NR_027932.1 link	n.305+730G>C	intron_variant	Intron 1 of 2
CLLU1	NR_027933.1 link	n.305+730G>C	intron_variant	Intron 1 of 1
CLLU1-AS1	NR_144319.2 link	n.91-1392C>G	intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
CLLU1	ENST00000472839.6 link	n.305+730G>C	intron_variant	Intron 1 of 2	1
CLLU1	ENST00000512817.1 link	n.305+730G>C	intron_variant	Intron 1 of 1	1
CLLU1	ENST00000589406.1 link	n.1035G>C	non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000523

AC:

AN:

248524

Hom.:

AF XY:

0.0000297

AC XY:

AN XY:

134580

show subpopulations

Gnomad AFR exome

AF:

0.000801

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000253

AC:

AN:

1461050

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

726818

show subpopulations

Gnomad4 AFR exome

AF:

0.000957

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.000263

AC:

AN:

152348

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.000962

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000568

Hom.:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000906

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.124C>G (p.L42V) 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 124, causing the leucine (L) at amino acid position 42 to be replaced by a valine (V). 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

0.17

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.59

CADD

Benign

2.7

DANN

Benign

0.97

DEOGEN2

Benign

0.083

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.0088

LIST_S2

Benign

0.42

M_CAP

Benign

0.0013

MetaRNN

Benign

0.015

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.044

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.55

Vest4

0.17

MVP

0.014

MPC

0.48

ClinPred

0.076

GERP RS

0.14

Varity_R

0.36

gMVP

0.0024

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over