1-111242504-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004000.3(CHI3L2):​c.*2+138C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 724,220 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: CHI3L2 NM_004000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000276 AC: 2 AN: 724220 Hom.: 0 Cov.: 10 AF XY: 0.00 AC XY: 0 AN XY: 361540

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 16784

American (AMR) AF: 0.00 AC: 0 AN: 15904

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14132

East Asian (EAS) AF: 0.00 AC: 0 AN: 29592

South Asian (SAS) AF: 0.00 AC: 0 AN: 33450

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31706

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2466

European-Non Finnish (NFE) AF: 0.00000366 AC: 2 AN: 546204

Other (OTH) AF: 0.00 AC: 0 AN: 33982

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.015
DANN	Benign	0.38
PhyloP100		-1.4

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;