19-19538939-G-C

Position:

• chr19-19538939-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153221.2(CILP2):​c.64+526G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,186 control chromosomes in the GnomAD database, including 6,018 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (6018 hom., cov: 33)
• Consequence: CILP2 NM_153221.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.561

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CILP2	NM_153221.2	c.64+526G>C		intron_variant		ENST00000291495.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CILP2	ENST00000291495.5	c.64+526G>C		intron_variant		1	NM_153221.2	P2
CILP2	ENST00000586018.5	c.64+526G>C		intron_variant		2		A1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 38065 AN: 152068 Hom.: 5994 Cov.: 33

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.0345

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.265

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.251 AC: 38128 AN: 152186 Hom.: 6018 Cov.: 33 AF XY: 0.247 AC XY: 18392 AN XY: 74402

Gnomad4 AFR AF: 0.439

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.0345

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.263

Alfa AF: 0.0818 Hom.: 92

Bravo AF: 0.265

Asia WGS AF: 0.153 AC: 532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.3
DANN	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs11670882; hg19: chr19-19649748; COSMIC: COSV52277639; COSMIC: COSV52277639;