1-111235846-G-A

Position:

• chr1-111235846-G-A

Variant summary

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

The NM_004000.3(CHI3L2):​c.605+83G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 1,573,172 control chromosomes in the GnomAD database, including 60,724 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 0.24 (4875 hom., cov: 33)
  • Exomes 𝑓: 0.28 (55849 hom.)
• Consequence: CHI3L2 NM_004000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.185

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHI3L2	NM_004000.3	c.605+83G>A		intron_variant		ENST00000369748.9
CHI3L2	NM_001025197.1	c.575+83G>A		intron_variant
CHI3L2	NM_001025199.2	c.368+83G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHI3L2	ENST00000369748.9	c.605+83G>A		intron_variant		1	NM_004000.3	P1

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36160 AN: 152052 Hom.: 4869 Cov.: 33

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.281

GnomAD4 exome AF: 0.278 AC: 394373 AN: 1421002 Hom.: 55849 Cov.: 29 AF XY: 0.278 AC XY: 195403 AN XY: 703618

Gnomad4 AFR exome AF: 0.106

Gnomad4 AMR exome AF: 0.307

Gnomad4 ASJ exome AF: 0.381

Gnomad4 EAS exome AF: 0.334

Gnomad4 SAS exome AF: 0.247

Gnomad4 FIN exome AF: 0.254

Gnomad4 NFE exome AF: 0.280

Gnomad4 OTH exome AF: 0.278

GnomAD4 genome AF: 0.238 AC: 36158 AN: 152170 Hom.: 4875 Cov.: 33 AF XY: 0.239 AC XY: 17808 AN XY: 74390

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.297

Gnomad4 ASJ AF: 0.359

Gnomad4 EAS AF: 0.326

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.279

Alfa AF: 0.287 Hom.: 6653

Bravo AF: 0.238

Asia WGS AF: 0.256 AC: 891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.7
DANN	Benign	0.61

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: rs961364; hg19: chr1-111778468;