dbSNP rs202214502: CILP2:p.Pro174Arg (chr19-19541175-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_153221.2(CILP2):c.521C>G(p.Pro174Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000158 in 1,265,502 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P174L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 9.0e-7 ( 0 hom. )

Consequence

CILP2
NM_153221.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.991

Publications

0 publications found

Variant links:

Genes affected

CILP2 (HGNC:24213): (cartilage intermediate layer protein 2) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

CILP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.08878636).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153221.2. 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
	CILP2	NM_153221.2	MANE Select	c.521C>G	p.Pro174Arg	missense	Exon 4 of 8	NP_694953.2	Q8IUL8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CILP2	ENST00000291495.5	TSL:1 MANE Select	c.521C>G	p.Pro174Arg	missense	Exon 4 of 8	ENSP00000291495.3	Q8IUL8
CILP2	ENST00000586018.5	TSL:2	c.539C>G	p.Pro180Arg	missense	Exon 4 of 8	ENSP00000467413.1	K7EPJ4
CILP2	ENST00000862972.1		c.518C>G	p.Pro173Arg	missense	Exon 4 of 8	ENSP00000533031.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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

GnomAD4 exome

AF:

8.98e-7

AC:

AN:

1113164

Hom.:

Cov.:

AF XY:

0.00000189

AC XY:

AN XY:

530398

show subpopulations

African (AFR)

AF:

0.0000418

AC:

AN:

23908

American (AMR)

AF:

0.00

AC:

AN:

11672

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14794

East Asian (EAS)

AF:

0.00

AC:

AN:

27922

South Asian (SAS)

AF:

0.00

AC:

AN:

26094

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24002

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3612

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

936322

Other (OTH)

AF:

0.00

AC:

AN:

44838

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

AF:

0.00000656

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41576

American (AMR)

AF:

0.00

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.024

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.62

M_CAP

Benign

0.025

MetaRNN

Benign

0.089

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.66

PhyloP100

0.99

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.51

REVEL

Benign

0.020

Sift

Benign

0.52

Sift4G

Benign

0.58

Polyphen

0.20

Vest4

0.28

MutPred

0.44

Gain of MoRF binding (P = 0.0013)

MVP

0.51

MPC

0.38

ClinPred

0.12

GERP RS

1.8

Varity_R

0.038

gMVP

0.40

Mutation Taster

=94/6

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