rs1056831

Positions:

• chr1-111243390-T-A

Variant summary

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

The NM_004000.3(CHI3L2):​c.*176T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 373,454 control chromosomes in the GnomAD database, including 15,657 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 0.25 (5594 hom., cov: 32)
  • Exomes 𝑓: 0.29 (10063 hom.)
• Consequence: CHI3L2 NM_004000.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.253

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHI3L2	NM_004000.3	c.*176T>A		3_prime_UTR_variant	11/11	ENST00000369748.9
CHI3L2	NM_001025197.1	c.*176T>A		3_prime_UTR_variant	10/10
CHI3L2	NM_001025199.2	c.*176T>A		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHI3L2	ENST00000369748.9	c.*176T>A		3_prime_UTR_variant	11/11	1	NM_004000.3	P1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37962 AN: 151958 Hom.: 5599 Cov.: 32

Gnomad AFR AF: 0.0970

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.278

GnomAD4 exome AF: 0.292 AC: 64668 AN: 221378 Hom.: 10063 Cov.: 0 AF XY: 0.286 AC XY: 35490 AN XY: 124184

Gnomad4 AFR exome AF: 0.0921

Gnomad4 AMR exome AF: 0.180

Gnomad4 ASJ exome AF: 0.325

Gnomad4 EAS exome AF: 0.184

Gnomad4 SAS exome AF: 0.224

Gnomad4 FIN exome AF: 0.339

Gnomad4 NFE exome AF: 0.339

Gnomad4 OTH exome AF: 0.312

GnomAD4 genome AF: 0.250 AC: 37954 AN: 152076 Hom.: 5594 Cov.: 32 AF XY: 0.246 AC XY: 18249 AN XY: 74304

Gnomad4 AFR AF: 0.0968

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.277

Alfa AF: 0.298 Hom.: 931

Bravo AF: 0.234

Asia WGS AF: 0.238 AC: 828 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.2
DANN	Benign	0.75

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: rs1056831; hg19: chr1-111786012;