1-111231208-A-T

Position:

• chr1-111231208-A-T

Variant summary

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

The NM_004000.3(CHI3L2):​c.273-30A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 1,564,546 control chromosomes in the GnomAD database, including 154,452 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 0.41 (13040 hom., cov: 32)
  • Exomes 𝑓: 0.44 (141412 hom.)
• Consequence: CHI3L2 NM_004000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.367

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHI3L2	NM_004000.3	c.273-30A>T		intron_variant		ENST00000369748.9	NP_003991.2
CHI3L2	NM_001025197.1	c.243-30A>T		intron_variant			NP_001020368.1
CHI3L2	NM_001025199.2	c.36-30A>T		intron_variant			NP_001020370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHI3L2	ENST00000369748.9	c.273-30A>T		intron_variant		1	NM_004000.3	ENSP00000358763	P1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61686 AN: 151932 Hom.: 13046 Cov.: 32

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.402

GnomAD3 exomes AF: 0.424 AC: 105511 AN: 248608 Hom.: 23233 AF XY: 0.430 AC XY: 57891 AN XY: 134492

Gnomad AFR exome AF: 0.293

Gnomad AMR exome AF: 0.278

Gnomad ASJ exome AF: 0.385

Gnomad EAS exome AF: 0.544

Gnomad SAS exome AF: 0.423

Gnomad FIN exome AF: 0.550

Gnomad NFE exome AF: 0.448

Gnomad OTH exome AF: 0.430

GnomAD4 exome AF: 0.443 AC: 626321 AN: 1412496 Hom.: 141412 Cov.: 23 AF XY: 0.443 AC XY: 312826 AN XY: 705804

Gnomad4 AFR exome AF: 0.292

Gnomad4 AMR exome AF: 0.289

Gnomad4 ASJ exome AF: 0.385

Gnomad4 EAS exome AF: 0.543

Gnomad4 SAS exome AF: 0.420

Gnomad4 FIN exome AF: 0.547

Gnomad4 NFE exome AF: 0.449

Gnomad4 OTH exome AF: 0.444

GnomAD4 genome AF: 0.406 AC: 61691 AN: 152050 Hom.: 13040 Cov.: 32 AF XY: 0.408 AC XY: 30323 AN XY: 74316

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.398

Gnomad4 EAS AF: 0.552

Gnomad4 SAS AF: 0.456

Gnomad4 FIN AF: 0.547

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.401

Alfa AF: 0.345 Hom.: 1554

Bravo AF: 0.386

Asia WGS AF: 0.486 AC: 1693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.5
DANN	Benign	0.81

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: rs2147789; hg19: chr1-111773830; COSMIC: COSV63873676; COSMIC: COSV63873676;