1-111242772-G-T

Position:

• chr1-111242772-G-T

Variant summary

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

The NM_004000.3(CHI3L2):​c.*2+406G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 164,418 control chromosomes in the GnomAD database, including 33,138 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 0.62 (30243 hom., cov: 31)
  • Exomes 𝑓: 0.68 (2895 hom.)
• Consequence: CHI3L2 NM_004000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21

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 (SAS) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHI3L2	NM_004000.3	c.*2+406G>T		intron_variant		ENST00000369748.9	NP_003991.2
CHI3L2	NM_001025197.1	c.*2+406G>T		intron_variant			NP_001020368.1
CHI3L2	NM_001025199.2	c.*2+406G>T		intron_variant			NP_001020370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHI3L2	ENST00000369748.9	c.*2+406G>T		intron_variant		1	NM_004000.3	ENSP00000358763.4

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94623 AN: 151806 Hom.: 30216 Cov.: 31

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.621

GnomAD4 exome AF: 0.676 AC: 8440 AN: 12494 Hom.: 2895 AF XY: 0.682 AC XY: 4453 AN XY: 6528

Gnomad4 AFR exome AF: 0.440

Gnomad4 AMR exome AF: 0.646

Gnomad4 ASJ exome AF: 0.600

Gnomad4 EAS exome AF: 0.633

Gnomad4 SAS exome AF: 0.734

Gnomad4 FIN exome AF: 0.679

Gnomad4 NFE exome AF: 0.685

Gnomad4 OTH exome AF: 0.679

GnomAD4 genome AF: 0.623 AC: 94703 AN: 151924 Hom.: 30243 Cov.: 31 AF XY: 0.626 AC XY: 46459 AN XY: 74264

Gnomad4 AFR AF: 0.477

Gnomad4 AMR AF: 0.636

Gnomad4 ASJ AF: 0.625

Gnomad4 EAS AF: 0.672

Gnomad4 SAS AF: 0.744

Gnomad4 FIN AF: 0.693

Gnomad4 NFE AF: 0.688

Gnomad4 OTH AF: 0.621

Alfa AF: 0.657 Hom.: 35614

Bravo AF: 0.608

Asia WGS AF: 0.700 AC: 2435 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	0.080
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs3934922; hg19: chr1-111785394; COSMIC: COSV63873734; COSMIC: COSV63873734;