1-111227969-A-G

Variant names:

• chr1-111227969-A-G
• rs2147790
• NM_004000.3:c.40+200A>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.40+200A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,278 control chromosomes in the GnomAD database, including 1,351 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 0.11 (1351 hom., cov: 32)
• Consequence: CHI3L2 NM_004000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHI3L2	NM_004000.3	c.40+200A>G		intron_variant	Intron 1 of 10	ENST00000369748.9	NP_003991.2
CHI3L2	NM_001025197.1	c.40+200A>G		intron_variant	Intron 1 of 9		NP_001020368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHI3L2	ENST00000369748.9	c.40+200A>G		intron_variant	Intron 1 of 10	1	NM_004000.3	ENSP00000358763.4

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17435 AN: 152160 Hom.: 1348 Cov.: 32

Gnomad AFR AF: 0.0290

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.0926

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.0806

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.0963

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

GnomAD4 genome AF: 0.115 AC: 17449 AN: 152278 Hom.: 1351 Cov.: 32 AF XY: 0.115 AC XY: 8531 AN XY: 74466

African (AFR) AF: 0.0290 AC: 1205 AN: 41564

American (AMR) AF: 0.205 AC: 3131 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 359 AN: 3470

East Asian (EAS) AF: 0.0928 AC: 481 AN: 5184

South Asian (SAS) AF: 0.152 AC: 733 AN: 4820

European-Finnish (FIN) AF: 0.0806 AC: 855 AN: 10614

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10288 AN: 68006

Other (OTH) AF: 0.0957 AC: 202 AN: 2110

Alfa AF: 0.136 Hom.: 2972

Bravo AF: 0.119

Asia WGS AF: 0.101 AC: 352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.83
DANN	Benign	0.56
PhyloP100		0.027
PromoterAI		0.081	Neutral
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: rs2147790; hg19: chr1-111770591;