rs35385195

Variant names:

• chr15-65197096-G-A
• rs35385195
• NM_003613.4:c.3190C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_003613.4(CILP):​c.3190C>T​(p.Leu1064Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0052 in 1,614,104 control chromosomes in the GnomAD database, including 382 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (195 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (187 hom.)
• Consequence: CILP NM_003613.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.58
• Publications: 0 publications found

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]

ENSG00000299580 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 15-65197096-G-A is Benign according to our data. Variant chr15-65197096-G-A is described in ClinVar as Benign. ClinVar VariationId is 785496.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.58 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0952 is higher than 0.05.

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.3190C>T	p.Leu1064Leu	synonymous	Exon 9 of 9	NP_003604.4	O75339

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CILP	ENST00000261883.6	TSL:1 MANE Select	c.3190C>T	p.Leu1064Leu	synonymous	Exon 9 of 9	ENSP00000261883.4	O75339
	CILP	ENST00000888802.1		c.3196C>T	p.Leu1066Leu	synonymous	Exon 9 of 9	ENSP00000558861.1
	CILP	ENST00000941157.1		c.3190C>T	p.Leu1064Leu	synonymous	Exon 9 of 9	ENSP00000611216.1

Frequencies

GnomAD3 genomes AF: 0.0277 AC: 4219 AN: 152188 Hom.: 193 Cov.: 32

Gnomad AFR AF: 0.0977

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00745

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0158

GnomAD2 exomes AF: 0.00723 AC: 1817 AN: 251170 AF XY: 0.00533

Gnomad AFR exome AF: 0.100

Gnomad AMR exome AF: 0.00338

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000432

Gnomad OTH exome AF: 0.00294

GnomAD4 exome AF: 0.00284 AC: 4155 AN: 1461798 Hom.: 187 Cov.: 78 AF XY: 0.00235 AC XY: 1711 AN XY: 727196

African (AFR) AF: 0.102 AC: 3430 AN: 33480

American (AMR) AF: 0.00389 AC: 174 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000220 AC: 19 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53366

Middle Eastern (MID) AF: 0.00503 AC: 29 AN: 5768

European-Non Finnish (NFE) AF: 0.000154 AC: 171 AN: 1111988

Other (OTH) AF: 0.00545 AC: 329 AN: 60396

GnomAD4 genome AF: 0.0278 AC: 4233 AN: 152306 Hom.: 195 Cov.: 32 AF XY: 0.0265 AC XY: 1973 AN XY: 74480

African (AFR) AF: 0.0977 AC: 4060 AN: 41540

American (AMR) AF: 0.00745 AC: 114 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68032

Other (OTH) AF: 0.0156 AC: 33 AN: 2110

Alfa AF: 0.0137 Hom.: 37

Bravo AF: 0.0316

Asia WGS AF: 0.00664 AC: 23 AN: 3478

EpiCase AF: 0.000600

EpiControl AF: 0.000889

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	6.7
DANN	Benign	0.71
PhyloP100		1.6
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

dbSNP: rs35385195; hg19: chr15-65489434;