1-111242504-C-T

Variant names:

• chr1-111242504-C-T
• rs6668814
• NM_004000.3:c.*2+138C>T

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+138C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.097 in 875,548 control chromosomes in the GnomAD database, including 6,074 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 0.090 (951 hom., cov: 32)
  • Exomes 𝑓: 0.099 (5123 hom.)
• Consequence: CHI3L2 NM_004000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHI3L2	NM_004000.3	c.*2+138C>T		intron_variant	Intron 10 of 10	ENST00000369748.9	NP_003991.2
CHI3L2	NM_001025197.1	c.*2+138C>T		intron_variant	Intron 9 of 9		NP_001020368.1
CHI3L2	NM_001025199.2	c.*2+138C>T		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+138C>T		intron_variant	Intron 10 of 10	1	NM_004000.3	ENSP00000358763.4

Frequencies

GnomAD3 genomes AF: 0.0898 AC: 13649 AN: 152050 Hom.: 958 Cov.: 32

Gnomad AFR AF: 0.0325

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0418

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0848

Gnomad OTH AF: 0.0794

GnomAD4 exome AF: 0.0986 AC: 71295 AN: 723380 Hom.: 5123 Cov.: 10 AF XY: 0.0991 AC XY: 35778 AN XY: 361124

African (AFR) AF: 0.0276 AC: 463 AN: 16778

American (AMR) AF: 0.0936 AC: 1488 AN: 15894

Ashkenazi Jewish (ASJ) AF: 0.0388 AC: 548 AN: 14122

East Asian (EAS) AF: 0.365 AC: 10787 AN: 29548

South Asian (SAS) AF: 0.151 AC: 5042 AN: 33374

European-Finnish (FIN) AF: 0.156 AC: 4929 AN: 31668

Middle Eastern (MID) AF: 0.0365 AC: 90 AN: 2466

European-Non Finnish (NFE) AF: 0.0824 AC: 44962 AN: 545578

Other (OTH) AF: 0.0879 AC: 2986 AN: 33952

GnomAD4 genome AF: 0.0897 AC: 13650 AN: 152168 Hom.: 951 Cov.: 32 AF XY: 0.0968 AC XY: 7205 AN XY: 74394

African (AFR) AF: 0.0326 AC: 1354 AN: 41522

American (AMR) AF: 0.102 AC: 1563 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0418 AC: 145 AN: 3472

East Asian (EAS) AF: 0.356 AC: 1837 AN: 5164

South Asian (SAS) AF: 0.185 AC: 894 AN: 4822

European-Finnish (FIN) AF: 0.176 AC: 1859 AN: 10582

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0848 AC: 5768 AN: 67998

Other (OTH) AF: 0.0795 AC: 168 AN: 2112

Alfa AF: 0.0886 Hom.: 298

Bravo AF: 0.0812

Asia WGS AF: 0.219 AC: 763 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.023
DANN	Benign	0.30
PhyloP100		-1.4
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: rs6668814; hg19: chr1-111785126;