rs961364

Variant names:

• chr1-111235846-G-A
• rs961364
• NM_004000.3:c.605+83G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004000.3(CHI3L2):​c.605+83G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 1,573,172 control chromosomes in the GnomAD database, including 60,724 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 0.24 (4875 hom., cov: 33)
  • Exomes 𝑓: 0.28 (55849 hom.)
• Consequence: CHI3L2 NM_004000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.185
• Publications: 8 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHI3L2	NM_004000.3	c.605+83G>A		intron_variant	Intron 6 of 10	ENST00000369748.9	NP_003991.2
CHI3L2	NM_001025197.1	c.575+83G>A		intron_variant	Intron 5 of 9		NP_001020368.1
CHI3L2	NM_001025199.2	c.368+83G>A		intron_variant	Intron 5 of 9		NP_001020370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHI3L2	ENST00000369748.9	c.605+83G>A		intron_variant	Intron 6 of 10	1	NM_004000.3	ENSP00000358763.4

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36160 AN: 152052 Hom.: 4869 Cov.: 33

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.281

GnomAD4 exome AF: 0.278 AC: 394373 AN: 1421002 Hom.: 55849 Cov.: 29 AF XY: 0.278 AC XY: 195403 AN XY: 703618

African (AFR) AF: 0.106 AC: 3434 AN: 32516

American (AMR) AF: 0.307 AC: 12946 AN: 42136

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 8994 AN: 23622

East Asian (EAS) AF: 0.334 AC: 13171 AN: 39412

South Asian (SAS) AF: 0.247 AC: 19616 AN: 79542

European-Finnish (FIN) AF: 0.254 AC: 13216 AN: 51968

Middle Eastern (MID) AF: 0.378 AC: 2114 AN: 5592

European-Non Finnish (NFE) AF: 0.280 AC: 304536 AN: 1087448

Other (OTH) AF: 0.278 AC: 16346 AN: 58766

GnomAD4 genome AF: 0.238 AC: 36158 AN: 152170 Hom.: 4875 Cov.: 33 AF XY: 0.239 AC XY: 17808 AN XY: 74390

African (AFR) AF: 0.112 AC: 4668 AN: 41524

American (AMR) AF: 0.297 AC: 4540 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1246 AN: 3472

East Asian (EAS) AF: 0.326 AC: 1688 AN: 5184

South Asian (SAS) AF: 0.240 AC: 1157 AN: 4816

European-Finnish (FIN) AF: 0.254 AC: 2685 AN: 10578

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 19070 AN: 67986

Other (OTH) AF: 0.279 AC: 589 AN: 2112

Alfa AF: 0.279 Hom.: 8275

Bravo AF: 0.238

Asia WGS AF: 0.256 AC: 891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.7
DANN	Benign	0.61
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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: rs961364; hg19: chr1-111778468;