rs2297950

Variant names:

• chr1-203225058-C-T
• rs2297950
• NM_003465.3:c.304G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003465.3(CHIT1):​c.304G>A​(p.Gly102Ser) variant causes a missense change. The variant allele was found at a frequency of 0.301 in 1,611,948 control chromosomes in the GnomAD database, including 73,780 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (6729 hom., cov: 30)
  • Exomes 𝑓: 0.30 (67051 hom.)
• Consequence: CHIT1 NM_003465.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:4 O:2
• Conservation: PhyloP100: 6.67
• Publications: 68 publications found

Genes affected

CHIT1 (HGNC:1936): (chitinase 1) Chitotriosidase is secreted by activated human macrophages and is markedly elevated in plasma of Gaucher disease patients. The expression of chitotriosidase occurs only at a late stage of differentiation of monocytes to activated macrophages in culture. Human macrophages can synthesize a functional chitotriosidase, a highly conserved enzyme with a strongly regulated expression. This enzyme may play a role in the degradation of chitin-containing pathogens. Several alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018247366).
• BP6: Variant 1-203225058-C-T is Benign according to our data. Variant chr1-203225058-C-T is described in ClinVar as Benign. ClinVar VariationId is 9526.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003465.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHIT1	NM_003465.3	MANE Select	c.304G>A	p.Gly102Ser	missense	Exon 4 of 11	NP_003456.1	Q13231-1
	CHIT1	NM_001256125.2		c.257+611G>A		intron	N/A	NP_001243054.2	Q13231-4
	CHIT1	NR_045784.2		n.341G>A		non_coding_transcript_exon	Exon 4 of 13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHIT1	ENST00000367229.6	TSL:1 MANE Select	c.304G>A	p.Gly102Ser	missense	Exon 4 of 11	ENSP00000356198.1	Q13231-1
	CHIT1	ENST00000491855.5	TSL:1	n.304G>A		non_coding_transcript_exon	Exon 4 of 12	ENSP00000423778.1	Q13231-2
	CHIT1	ENST00000503786.1	TSL:1	n.304G>A		non_coding_transcript_exon	Exon 4 of 13	ENSP00000421617.1	D6REY1

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45014 AN: 151466 Hom.: 6716 Cov.: 30

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.299

GnomAD2 exomes AF: 0.305 AC: 76573 AN: 251020 AF XY: 0.301

Gnomad AFR exome AF: 0.269

Gnomad AMR exome AF: 0.365

Gnomad ASJ exome AF: 0.323

Gnomad EAS exome AF: 0.274

Gnomad FIN exome AF: 0.318

Gnomad NFE exome AF: 0.303

Gnomad OTH exome AF: 0.298

GnomAD4 exome AF: 0.301 AC: 440170 AN: 1460362 Hom.: 67051 Cov.: 34 AF XY: 0.300 AC XY: 218266 AN XY: 726572

African (AFR) AF: 0.264 AC: 8848 AN: 33462

American (AMR) AF: 0.360 AC: 16091 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 8653 AN: 26120

East Asian (EAS) AF: 0.285 AC: 11317 AN: 39680

South Asian (SAS) AF: 0.264 AC: 22783 AN: 86208

European-Finnish (FIN) AF: 0.318 AC: 16941 AN: 53342

Middle Eastern (MID) AF: 0.242 AC: 1392 AN: 5758

European-Non Finnish (NFE) AF: 0.303 AC: 336474 AN: 1110766

Other (OTH) AF: 0.293 AC: 17671 AN: 60346

GnomAD4 genome AF: 0.297 AC: 45064 AN: 151586 Hom.: 6729 Cov.: 30 AF XY: 0.298 AC XY: 22062 AN XY: 74026

African (AFR) AF: 0.270 AC: 11145 AN: 41270

American (AMR) AF: 0.305 AC: 4643 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1160 AN: 3468

East Asian (EAS) AF: 0.268 AC: 1370 AN: 5104

South Asian (SAS) AF: 0.258 AC: 1241 AN: 4812

European-Finnish (FIN) AF: 0.335 AC: 3516 AN: 10482

Middle Eastern (MID) AF: 0.216 AC: 63 AN: 292

European-Non Finnish (NFE) AF: 0.311 AC: 21095 AN: 67902

Other (OTH) AF: 0.302 AC: 638 AN: 2110

Alfa AF: 0.304 Hom.: 28643

Bravo AF: 0.294

TwinsUK AF: 0.297 AC: 1103

ALSPAC AF: 0.300 AC: 1157

ESP6500AA AF: 0.270 AC: 1188

ESP6500EA AF: 0.293 AC: 2522

ExAC AF: 0.303 AC: 36751

Asia WGS AF: 0.296 AC: 1026 AN: 3478

EpiCase AF: 0.299

EpiControl AF: 0.283

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	2	not provided (4)
-	-	2	Chitotriosidase deficiency (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.33
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Pathogenic	0.98	D
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.8	L
PhyloP100		6.7
PrimateAI	Benign	0.34	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Benign	0.23
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.20
MPC		0.46
ClinPred		0.026	T
GERP RS		2.6
Varity_R		0.80
gMVP		0.72
Mutation Taster		=90/10	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: rs2297950; hg19: chr1-203194186; COSMIC: COSV55145538; COSMIC: COSV55145538;