rs1077059

Variant names:

• chr1-111242473-C-G
• rs1077059
• NM_004000.3:c.*2+107C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004000.3(CHI3L2):​c.*2+107C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0304 in 1,234,760 control chromosomes in the GnomAD database, including 1,436 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 0.065 (723 hom., cov: 32)
  • Exomes 𝑓: 0.026 (713 hom.)
• Consequence: CHI3L2 NM_004000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.746
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHI3L2	NM_004000.3	c.*2+107C>G		intron_variant	Intron 10 of 10	ENST00000369748.9	NP_003991.2
CHI3L2	NM_001025197.1	c.*2+107C>G		intron_variant	Intron 9 of 9		NP_001020368.1
CHI3L2	NM_001025199.2	c.*2+107C>G		intron_variant	Intron 9 of 9		NP_001020370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHI3L2	ENST00000369748.9	c.*2+107C>G		intron_variant	Intron 10 of 10	1	NM_004000.3	ENSP00000358763.4

Frequencies

GnomAD3 genomes AF: 0.0649 AC: 9872 AN: 152054 Hom.: 723 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0328

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00973

Gnomad FIN AF: 0.0503

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0209

Gnomad OTH AF: 0.0468

GnomAD4 exome AF: 0.0256 AC: 27677 AN: 1082588 Hom.: 713 Cov.: 14 AF XY: 0.0249 AC XY: 13270 AN XY: 532528

African (AFR) AF: 0.178 AC: 4255 AN: 23864

American (AMR) AF: 0.0341 AC: 758 AN: 22224

Ashkenazi Jewish (ASJ) AF: 0.00592 AC: 100 AN: 16884

East Asian (EAS) AF: 0.000118 AC: 4 AN: 34026

South Asian (SAS) AF: 0.0110 AC: 525 AN: 47712

European-Finnish (FIN) AF: 0.0466 AC: 1848 AN: 39678

Middle Eastern (MID) AF: 0.0246 AC: 76 AN: 3092

European-Non Finnish (NFE) AF: 0.0220 AC: 18678 AN: 849146

Other (OTH) AF: 0.0312 AC: 1433 AN: 45962

GnomAD4 genome AF: 0.0649 AC: 9881 AN: 152172 Hom.: 723 Cov.: 32 AF XY: 0.0642 AC XY: 4772 AN XY: 74374

African (AFR) AF: 0.175 AC: 7247 AN: 41460

American (AMR) AF: 0.0327 AC: 500 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.00953 AC: 46 AN: 4828

European-Finnish (FIN) AF: 0.0503 AC: 532 AN: 10586

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0209 AC: 1424 AN: 68024

Other (OTH) AF: 0.0464 AC: 98 AN: 2114

Alfa AF: 0.0449 Hom.: 41

Bravo AF: 0.0700

Asia WGS AF: 0.0200 AC: 68 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	2.0
DANN	Benign	0.86
PhyloP100		-0.75
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1077059; hg19: chr1-111785095;