1-111227801-T-G

Position:

• chr1-111227801-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004000.3(CHI3L2):​c.40+32T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 1,606,608 control chromosomes in the GnomAD database, including 410,160 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 0.70 (37048 hom., cov: 32)
  • Exomes 𝑓: 0.72 (373112 hom.)
• Consequence: CHI3L2 NM_004000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.125

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHI3L2	NM_004000.3	c.40+32T>G		intron_variant		ENST00000369748.9	NP_003991.2
CHI3L2	NM_001025197.1	c.40+32T>G		intron_variant			NP_001020368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHI3L2	ENST00000369748.9	c.40+32T>G		intron_variant		1	NM_004000.3	ENSP00000358763.4

Frequencies

GnomAD3 genomes AF: 0.697 AC: 105933 AN: 151966 Hom.: 37003 Cov.: 32

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.672

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.759

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.719

Gnomad OTH AF: 0.674

GnomAD3 exomes AF: 0.707 AC: 177464 AN: 251138 Hom.: 62863 AF XY: 0.708 AC XY: 96131 AN XY: 135712

Gnomad AFR exome AF: 0.663

Gnomad AMR exome AF: 0.684

Gnomad ASJ exome AF: 0.617

Gnomad EAS exome AF: 0.653

Gnomad SAS exome AF: 0.755

Gnomad FIN exome AF: 0.749

Gnomad NFE exome AF: 0.716

Gnomad OTH exome AF: 0.696

GnomAD4 exome AF: 0.715 AC: 1040352 AN: 1454524 Hom.: 373112 Cov.: 30 AF XY: 0.716 AC XY: 518500 AN XY: 724168

Gnomad4 AFR exome AF: 0.653

Gnomad4 AMR exome AF: 0.680

Gnomad4 ASJ exome AF: 0.617

Gnomad4 EAS exome AF: 0.662

Gnomad4 SAS exome AF: 0.753

Gnomad4 FIN exome AF: 0.747

Gnomad4 NFE exome AF: 0.719

Gnomad4 OTH exome AF: 0.705

GnomAD4 genome AF: 0.697 AC: 106032 AN: 152084 Hom.: 37048 Cov.: 32 AF XY: 0.698 AC XY: 51884 AN XY: 74348

Gnomad4 AFR AF: 0.662

Gnomad4 AMR AF: 0.672

Gnomad4 ASJ AF: 0.637

Gnomad4 EAS AF: 0.668

Gnomad4 SAS AF: 0.760

Gnomad4 FIN AF: 0.747

Gnomad4 NFE AF: 0.719

Gnomad4 OTH AF: 0.673

Alfa AF: 0.701 Hom.: 50708

Bravo AF: 0.686

Asia WGS AF: 0.722 AC: 2509 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.9
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs755467; hg19: chr1-111770423; COSMIC: COSV63873665; COSMIC: COSV63873665;