1-111230978-A-G

Position:

• chr1-111230978-A-G

Variant summary

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

The NM_004000.3(CHI3L2):​c.272+35A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0996 in 1,554,704 control chromosomes in the GnomAD database, including 10,175 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 0.096 (980 hom., cov: 32)
  • Exomes 𝑓: 0.10 (9195 hom.)
• Consequence: CHI3L2 NM_004000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.919

Genes affected

CHI3L2 (HGNC:1933): (chitinase 3 like 2) The protein encoded by this gene is similar to bacterial chitinases but lacks chitinase activity. The encoded protein is secreted and is involved in cartilage biogenesis. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

CHI3L2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHI3L2	NM_004000.3	c.272+35A>G		intron_variant		ENST00000369748.9	NP_003991.2
CHI3L2	NM_001025197.1	c.242+35A>G		intron_variant			NP_001020368.1
CHI3L2	NM_001025199.2	c.35+35A>G		intron_variant			NP_001020370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHI3L2	ENST00000369748.9	c.272+35A>G		intron_variant		1	NM_004000.3	ENSP00000358763.4

Frequencies

GnomAD3 genomes AF: 0.0965 AC: 14672 AN: 152058 Hom.: 986 Cov.: 32

Gnomad AFR AF: 0.0560

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0421

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0851

Gnomad OTH AF: 0.0837

GnomAD3 exomes AF: 0.120 AC: 28834 AN: 241226 Hom.: 2452 AF XY: 0.120 AC XY: 15551 AN XY: 130122

Gnomad AFR exome AF: 0.0557

Gnomad AMR exome AF: 0.0983

Gnomad ASJ exome AF: 0.0421

Gnomad EAS exome AF: 0.358

Gnomad SAS exome AF: 0.159

Gnomad FIN exome AF: 0.170

Gnomad NFE exome AF: 0.0841

Gnomad OTH exome AF: 0.0917

GnomAD4 exome AF: 0.100 AC: 140199 AN: 1402528 Hom.: 9195 Cov.: 22 AF XY: 0.101 AC XY: 70663 AN XY: 700054

Gnomad4 AFR exome AF: 0.0501

Gnomad4 AMR exome AF: 0.0992

Gnomad4 ASJ exome AF: 0.0400

Gnomad4 EAS exome AF: 0.366

Gnomad4 SAS exome AF: 0.157

Gnomad4 FIN exome AF: 0.159

Gnomad4 NFE exome AF: 0.0861

Gnomad4 OTH exome AF: 0.0961

GnomAD4 genome AF: 0.0965 AC: 14678 AN: 152176 Hom.: 980 Cov.: 32 AF XY: 0.103 AC XY: 7666 AN XY: 74388

Gnomad4 AFR AF: 0.0561

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.0421

Gnomad4 EAS AF: 0.350

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.0851

Gnomad4 OTH AF: 0.0838

Alfa AF: 0.0786 Hom.: 765

Bravo AF: 0.0890

Asia WGS AF: 0.221 AC: 769 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.46

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

LitVar

Other links and lift over

dbSNP: rs2274232; hg19: chr1-111773600; COSMIC: COSV63873603; COSMIC: COSV63873603;