rs2486958

Positions:

• chr1-203219564-A-C
• chr1-203219564-A-G
• chr1-203219564-A-T

Variant summary

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

The NM_003465.3(CHIT1):​c.915+100T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 1,376,092 control chromosomes in the GnomAD database, including 204,971 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 0.54 (23084 hom., cov: 32)
  • Exomes 𝑓: 0.53 (181887 hom.)
• Consequence: CHIT1 NM_003465.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.264

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHIT1	NM_003465.3	c.915+100T>G		intron_variant		ENST00000367229.6	NP_003456.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHIT1	ENST00000367229.6	c.915+100T>G		intron_variant		1	NM_003465.3	ENSP00000356198	P1

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82447 AN: 151998 Hom.: 23049 Cov.: 32

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.934

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.556

GnomAD4 exome AF: 0.534 AC: 653761 AN: 1223976 Hom.: 181887 Cov.: 17 AF XY: 0.538 AC XY: 333496 AN XY: 619670

Gnomad4 AFR exome AF: 0.520

Gnomad4 AMR exome AF: 0.747

Gnomad4 ASJ exome AF: 0.565

Gnomad4 EAS exome AF: 0.953

Gnomad4 SAS exome AF: 0.693

Gnomad4 FIN exome AF: 0.475

Gnomad4 NFE exome AF: 0.494

Gnomad4 OTH exome AF: 0.537

GnomAD4 genome AF: 0.543 AC: 82540 AN: 152116 Hom.: 23084 Cov.: 32 AF XY: 0.550 AC XY: 40932 AN XY: 74374

Gnomad4 AFR AF: 0.530

Gnomad4 AMR AF: 0.640

Gnomad4 ASJ AF: 0.558

Gnomad4 EAS AF: 0.935

Gnomad4 SAS AF: 0.715

Gnomad4 FIN AF: 0.490

Gnomad4 NFE AF: 0.496

Gnomad4 OTH AF: 0.559

Alfa AF: 0.502 Hom.: 17810

Bravo AF: 0.550

Asia WGS AF: 0.810 AC: 2811 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.52

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: rs2486958; hg19: chr1-203188692;