NM_004000.3:c.*2+406G>T

Variant names:

• chr1-111242772-G-T
• rs3934922
• NM_004000.3:c.*2+406G>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+406G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 164,418 control chromosomes in the GnomAD database, including 33,138 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 0.62 (30243 hom., cov: 31)
  • Exomes 𝑓: 0.68 (2895 hom.)
• Consequence: CHI3L2 NM_004000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHI3L2	NM_004000.3	c.*2+406G>T		intron_variant	Intron 10 of 10	ENST00000369748.9	NP_003991.2
CHI3L2	NM_001025197.1	c.*2+406G>T		intron_variant	Intron 9 of 9		NP_001020368.1
CHI3L2	NM_001025199.2	c.*2+406G>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+406G>T		intron_variant	Intron 10 of 10	1	NM_004000.3	ENSP00000358763.4

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94623 AN: 151806 Hom.: 30216 Cov.: 31

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.621

GnomAD4 exome AF: 0.676 AC: 8440 AN: 12494 Hom.: 2895 AF XY: 0.682 AC XY: 4453 AN XY: 6528

African (AFR) AF: 0.440 AC: 81 AN: 184

American (AMR) AF: 0.646 AC: 1524 AN: 2358

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 108 AN: 180

East Asian (EAS) AF: 0.633 AC: 457 AN: 722

South Asian (SAS) AF: 0.734 AC: 1165 AN: 1588

European-Finnish (FIN) AF: 0.679 AC: 144 AN: 212

Middle Eastern (MID) AF: 0.567 AC: 17 AN: 30

European-Non Finnish (NFE) AF: 0.685 AC: 4606 AN: 6722

Other (OTH) AF: 0.679 AC: 338 AN: 498

GnomAD4 genome AF: 0.623 AC: 94703 AN: 151924 Hom.: 30243 Cov.: 31 AF XY: 0.626 AC XY: 46459 AN XY: 74264

African (AFR) AF: 0.477 AC: 19743 AN: 41396

American (AMR) AF: 0.636 AC: 9726 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.625 AC: 2169 AN: 3468

East Asian (EAS) AF: 0.672 AC: 3466 AN: 5160

South Asian (SAS) AF: 0.744 AC: 3584 AN: 4814

European-Finnish (FIN) AF: 0.693 AC: 7306 AN: 10540

Middle Eastern (MID) AF: 0.534 AC: 155 AN: 290

European-Non Finnish (NFE) AF: 0.688 AC: 46732 AN: 67952

Other (OTH) AF: 0.621 AC: 1310 AN: 2110

Alfa AF: 0.651 Hom.: 50176

Bravo AF: 0.608

Asia WGS AF: 0.700 AC: 2435 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	0.080
DANN	Benign	0.77
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs3934922; hg19: chr1-111785394; COSMIC: COSV63873734; COSMIC: COSV63873734;