rs12048900

Positions:

• chr1-111223429-A-T

Variant summary

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

The ENST00000445067.6(CHI3L2):​c.-156-2515A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 152,070 control chromosomes in the GnomAD database, including 9,222 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 0.34 (9222 hom., cov: 32)
• Consequence: CHI3L2 ENST00000445067.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.482

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHI3L2	ENST00000445067.6	c.-156-2515A>T		intron_variant		5		ENSP00000437082	P1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52121 AN: 151952 Hom.: 9225 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.353

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.343 AC: 52131 AN: 152070 Hom.: 9222 Cov.: 32 AF XY: 0.338 AC XY: 25086 AN XY: 74320

Gnomad4 AFR AF: 0.298

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.394

Gnomad4 NFE AF: 0.391

Gnomad4 OTH AF: 0.351

Alfa AF: 0.372 Hom.: 1335

Bravo AF: 0.331

Asia WGS AF: 0.269 AC: 936 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.77

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: rs12048900; hg19: chr1-111766051;