19-19539680-C-T

Variant names:

• chr19-19539680-C-T
• rs773143828
• NM_153221.2:c.66C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_153221.2(CILP2):​c.66C>T​(p.Asp22Asp) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,428,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CILP2 NM_153221.2 splice_region, synonymous
• Scores: Splicing: ADA: 0.00006321
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.628
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-0.628 with no splicing effect.

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.66C>T	p.Asp22Asp	splice_region synonymous	Exon 2 of 8	NP_694953.2	Q8IUL8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CILP2	ENST00000291495.5	TSL:1 MANE Select	c.66C>T	p.Asp22Asp	splice_region synonymous	Exon 2 of 8	ENSP00000291495.3	Q8IUL8
	CILP2	ENST00000586018.5	TSL:2	c.66C>T	p.Asp22Asp	splice_region synonymous	Exon 2 of 8	ENSP00000467413.1	K7EPJ4
	CILP2	ENST00000862972.1		c.66C>T	p.Asp22Asp	splice_region synonymous	Exon 2 of 8	ENSP00000533031.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1428746 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 710164

African (AFR) AF: 0.00 AC: 0 AN: 31430

American (AMR) AF: 0.00 AC: 0 AN: 41652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24942

East Asian (EAS) AF: 0.00 AC: 0 AN: 37130

South Asian (SAS) AF: 0.00 AC: 0 AN: 82698

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52472

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5628

European-Non Finnish (NFE) AF: 9.14e-7 AC: 1 AN: 1094016

Other (OTH) AF: 0.00 AC: 0 AN: 58778

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000285 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.0
DANN	Benign	0.85
PhyloP100		-0.63
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000063
dbscSNV1_RF	Benign	0.0
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: rs773143828; hg19: chr19-19650489; COSMIC: COSV52277445; COSMIC: COSV52277445;