1-111231208-A-T

Variant names:

• chr1-111231208-A-T
• rs2147789
• NM_004000.3:c.273-30A>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.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
• Publications: 10 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=-0.82).
• 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 rank	MANE	Protein	UniProt
CHI3L2	NM_004000.3	c.273-30A>T		intron_variant	Intron 3 of 10	ENST00000369748.9	NP_003991.2
CHI3L2	NM_001025197.1	c.243-30A>T		intron_variant	Intron 2 of 9		NP_001020368.1
CHI3L2	NM_001025199.2	c.36-30A>T		intron_variant	Intron 2 of 9		NP_001020370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHI3L2	ENST00000369748.9	c.273-30A>T		intron_variant	Intron 3 of 10	1	NM_004000.3	ENSP00000358763.4

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

GnomAD2 exomes AF: 0.424 AC: 105511 AN: 248608 AF XY: 0.430

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 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

African (AFR) AF: 0.292 AC: 9469 AN: 32390

American (AMR) AF: 0.289 AC: 12750 AN: 44074

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 9937 AN: 25792

East Asian (EAS) AF: 0.543 AC: 21404 AN: 39444

South Asian (SAS) AF: 0.420 AC: 35673 AN: 84838

European-Finnish (FIN) AF: 0.547 AC: 29175 AN: 53336

Middle Eastern (MID) AF: 0.351 AC: 1989 AN: 5664

European-Non Finnish (NFE) AF: 0.449 AC: 479891 AN: 1068312

Other (OTH) AF: 0.444 AC: 26033 AN: 58646

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

African (AFR) AF: 0.301 AC: 12486 AN: 41438

American (AMR) AF: 0.354 AC: 5407 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1380 AN: 3466

East Asian (EAS) AF: 0.552 AC: 2855 AN: 5170

South Asian (SAS) AF: 0.456 AC: 2195 AN: 4818

European-Finnish (FIN) AF: 0.547 AC: 5784 AN: 10568

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.447 AC: 30404 AN: 67986

Other (OTH) AF: 0.401 AC: 843 AN: 2104

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
PhyloP100		0.37
PromoterAI		-0.00060	Neutral
Mutation Taster		=6/94	disease causing

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

Other links and lift over

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