rs6685226

Positions:

• chr1-111237982-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.736-768A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,174 control chromosomes in the GnomAD database, including 1,998 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 0.16 (1998 hom., cov: 32)
• Consequence: CHI3L2 NM_004000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHI3L2	NM_004000.3	c.736-768A>G		intron_variant		ENST00000369748.9
CHI3L2	NM_001025197.1	c.706-768A>G		intron_variant
CHI3L2	NM_001025199.2	c.499-768A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHI3L2	ENST00000369748.9	c.736-768A>G		intron_variant		1	NM_004000.3	P1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23879 AN: 152056 Hom.: 1991 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.0922

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.0787

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.157 AC: 23919 AN: 152174 Hom.: 1998 Cov.: 32 AF XY: 0.155 AC XY: 11507 AN XY: 74412

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.0924

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.0787

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.125

Alfa AF: 0.173 Hom.: 404

Bravo AF: 0.168

Asia WGS AF: 0.115 AC: 399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.2
DANN	Benign	0.66

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: rs6685226; hg19: chr1-111780604;