rs2477574

chr1-111237792-G-Achr1-111237792-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.736-958G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 152,114 control chromosomes in the GnomAD database, including 10,220 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 0.34 (10220 hom., cov: 32)
• Consequence: CHI3L2 NM_004000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHI3L2	NM_004000.3	c.736-958G>A		intron_variant		ENST00000369748.9
CHI3L2	NM_001025197.1	c.706-958G>A		intron_variant
CHI3L2	NM_001025199.2	c.499-958G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHI3L2	ENST00000369748.9	c.736-958G>A		intron_variant		1	NM_004000.3	P1

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51621 AN: 151996 Hom.: 10230 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.339 AC: 51614 AN: 152114 Hom.: 10220 Cov.: 32 AF XY: 0.343 AC XY: 25486 AN XY: 74356

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.423

Gnomad4 FIN AF: 0.499

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.356

Alfa AF: 0.363 Hom.: 1867

Bravo AF: 0.315

Asia WGS AF: 0.458 AC: 1593 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	1.3
Dann	Benign	0.50

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: rs2477574; hg19: chr1-111780414;