rs2486958

Variant names:

• chr1-203219564-A-C
• rs2486958
• NM_003465.3:c.915+100T>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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 -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.

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.915+100T>G		intron	N/A	NP_003456.1	Q13231-1
	CHIT1	NM_001256125.2		c.858+100T>G		intron	N/A	NP_001243054.2	Q13231-4
	CHIT1	NR_045784.2		n.952+100T>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHIT1	ENST00000367229.6	TSL:1 MANE Select	c.915+100T>G		intron	N/A	ENSP00000356198.1	Q13231-1
	CHIT1	ENST00000491855.5	TSL:1	n.915+100T>G		intron	N/A	ENSP00000423778.1	Q13231-2
	CHIT1	ENST00000503786.1	TSL:1	n.915+100T>G		intron	N/A	ENSP00000421617.1	D6REY1

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

African (AFR) AF: 0.520 AC: 14987 AN: 28802

American (AMR) AF: 0.747 AC: 33114 AN: 44336

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 13922 AN: 24624

East Asian (EAS) AF: 0.953 AC: 36753 AN: 38558

South Asian (SAS) AF: 0.693 AC: 56112 AN: 80972

European-Finnish (FIN) AF: 0.475 AC: 24816 AN: 52276

Middle Eastern (MID) AF: 0.518 AC: 2722 AN: 5254

European-Non Finnish (NFE) AF: 0.494 AC: 443160 AN: 896722

Other (OTH) AF: 0.537 AC: 28175 AN: 52432

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

African (AFR) AF: 0.530 AC: 21989 AN: 41484

American (AMR) AF: 0.640 AC: 9791 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1938 AN: 3472

East Asian (EAS) AF: 0.935 AC: 4847 AN: 5186

South Asian (SAS) AF: 0.715 AC: 3454 AN: 4832

European-Finnish (FIN) AF: 0.490 AC: 5184 AN: 10578

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33714 AN: 67958

Other (OTH) AF: 0.559 AC: 1180 AN: 2110

Alfa AF: 0.515 Hom.: 28541

Bravo AF: 0.550

Asia WGS AF: 0.810 AC: 2811 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.52
PhyloP100		-0.26
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: rs2486958; hg19: chr1-203188692;