rs73066394

Variant names:

• chr1-203216355-A-C
• rs73066394
• NM_003465.3:c.*534T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-203216355-A-C
• chr1-203216355-A-G
• chr1-203216355-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003465.3(CHIT1):​c.*534T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0284 in 454,014 control chromosomes in the GnomAD database, including 1,293 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.066 (1083 hom., cov: 33)
  • Exomes 𝑓: 0.0096 (210 hom.)
• Consequence: CHIT1 NM_003465.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.972
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-203216355-A-C is Benign according to our data. Variant chr1-203216355-A-C is described in ClinVar as Benign. ClinVar VariationId is 294902.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.221 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.*534T>G		3_prime_UTR	Exon 11 of 11	NP_003456.1	Q13231-1
	CHIT1	NM_001256125.2		c.*534T>G		3_prime_UTR	Exon 10 of 10	NP_001243054.2	Q13231-4
	CHIT1	NR_045784.2		n.2200T>G		non_coding_transcript_exon	Exon 13 of 13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHIT1	ENST00000367229.6	TSL:1 MANE Select	c.*534T>G		3_prime_UTR	Exon 11 of 11	ENSP00000356198.1	Q13231-1
	CHIT1	ENST00000479483.1	TSL:3	n.283+1384T>G		intron	N/A
	CHIT1	ENST00000484834.5	TSL:2	n.5388+1384T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0655 AC: 9959 AN: 152088 Hom.: 1075 Cov.: 33

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0288

Gnomad ASJ AF: 0.00951

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00126

Gnomad OTH AF: 0.0588

GnomAD2 exomes AF: 0.0154 AC: 2003 AN: 130214 AF XY: 0.0120

Gnomad AFR exome AF: 0.232

Gnomad AMR exome AF: 0.0161

Gnomad ASJ exome AF: 0.0100

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00123

Gnomad OTH exome AF: 0.00999

GnomAD4 exome AF: 0.00958 AC: 2892 AN: 301808 Hom.: 210 Cov.: 0 AF XY: 0.00723 AC XY: 1243 AN XY: 172006

African (AFR) AF: 0.226 AC: 1936 AN: 8554

American (AMR) AF: 0.0157 AC: 427 AN: 27274

Ashkenazi Jewish (ASJ) AF: 0.00955 AC: 103 AN: 10786

East Asian (EAS) AF: 0.00 AC: 0 AN: 9210

South Asian (SAS) AF: 0.000821 AC: 49 AN: 59650

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12366

Middle Eastern (MID) AF: 0.0200 AC: 23 AN: 1150

European-Non Finnish (NFE) AF: 0.000655 AC: 104 AN: 158776

Other (OTH) AF: 0.0178 AC: 250 AN: 14042

GnomAD4 genome AF: 0.0657 AC: 10002 AN: 152206 Hom.: 1083 Cov.: 33 AF XY: 0.0633 AC XY: 4715 AN XY: 74432

African (AFR) AF: 0.224 AC: 9309 AN: 41480

American (AMR) AF: 0.0288 AC: 440 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00951 AC: 33 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00126 AC: 86 AN: 68018

Other (OTH) AF: 0.0587 AC: 124 AN: 2114

Alfa AF: 0.0349 Hom.: 206

Bravo AF: 0.0753

Asia WGS AF: 0.0140 AC: 51 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Chitotriosidase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.51
DANN	Benign	0.41
PhyloP100		-0.97
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs73066394; hg19: chr1-203185483;