Genetic Variant NM_003613.4:c.2941G>A (chr15-65197345-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_003613.4(CILP):c.2941G>A(p.Val981Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,860 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: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CILP
NM_003613.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.06

Publications

0 publications found

Variant links:

Genes affected

CILP (HGNC:1980): (cartilage intermediate layer protein) Major alterations in the composition of the cartilage extracellular matrix occur in joint disease, such as osteoarthrosis. This gene encodes the cartilage intermediate layer protein (CILP), which increases in early osteoarthrosis cartilage. The encoded protein was thought to encode a protein precursor for two different proteins; an N-terminal CILP and a C-terminal homolog of NTPPHase, however, later studies identified no nucleotide pyrophosphatase phosphodiesterase (NPP) activity. The full-length and the N-terminal domain of this protein was shown to function as an IGF-1 antagonist. An allelic variant of this gene has been associated with lumbar disc disease. [provided by RefSeq, Sep 2010]

CILP links:

ENSG00000299580 (HGNC:):

ENSG00000299580 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3547101).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003613.4. 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
	CILP	NM_003613.4	MANE Select	c.2941G>A	p.Val981Met	missense	Exon 9 of 9	NP_003604.4	O75339

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CILP	ENST00000261883.6	TSL:1 MANE Select	c.2941G>A	p.Val981Met	missense	Exon 9 of 9	ENSP00000261883.4	O75339
CILP	ENST00000888802.1		c.2947G>A	p.Val983Met	missense	Exon 9 of 9	ENSP00000558861.1
CILP	ENST00000941157.1		c.2941G>A	p.Val981Met	missense	Exon 9 of 9	ENSP00000611216.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461860

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727226

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111998

Other (OTH)

AF:

0.0000166

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.090

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.0029

MetaRNN

Benign

0.35

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.6

PhyloP100

4.1

PrimateAI

Uncertain

0.61

PROVEAN

Benign

0.070

REVEL

Benign

0.076

Sift

Benign

0.11

Sift4G

Benign

0.14

Polyphen

0.98

Vest4

0.33

MutPred

0.21

Gain of disorder (P = 0.0553)

MVP

0.59

MPC

0.43

ClinPred

0.91

GERP RS

5.6

Varity_R

0.057

gMVP

0.47

Mutation Taster

=88/12

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over