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GeneBe

1-111315429-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_201653.4(CHIA):c.474G>C(p.Leu158=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000697 in 1,612,088 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0010 ( 2 hom., cov: 31)
Exomes 𝑓: 0.00066 ( 18 hom. )

Consequence

CHIA
NM_201653.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.170
Variant links:
Genes affected
CHIA (HGNC:17432): (chitinase acidic) The protein encoded by this gene degrades chitin, which is found in the cell wall of most fungi as well as in arthropods and some nematodes. The encoded protein can also stimulate interleukin 13 expression, and variations in this gene can lead to asthma susceptibility. Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-111315429-G-C is Benign according to our data. Variant chr1-111315429-G-C is described in ClinVar as [Benign]. Clinvar id is 720744.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.17 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00103 (157/152296) while in subpopulation EAS AF= 0.0195 (101/5190). AF 95% confidence interval is 0.0164. There are 2 homozygotes in gnomad4. There are 75 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CHIANM_201653.4 linkuse as main transcriptc.474G>C p.Leu158= synonymous_variant 6/12 ENST00000369740.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CHIAENST00000369740.6 linkuse as main transcriptc.474G>C p.Leu158= synonymous_variant 6/121 NM_201653.4 P1Q9BZP6-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00104
AC:
159
AN:
152178
Hom.:
2
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00124
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0198
Gnomad SAS
AF:
0.00269
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.000957
GnomAD3 exomes
AF:
0.00205
AC:
510
AN:
248812
Hom.:
3
AF XY:
0.00190
AC XY:
256
AN XY:
134396
show subpopulations
Gnomad AFR exome
AF:
0.000432
Gnomad AMR exome
AF:
0.000205
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0248
Gnomad SAS exome
AF:
0.000964
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000178
Gnomad OTH exome
AF:
0.00181
GnomAD4 exome
AF:
0.000662
AC:
967
AN:
1459792
Hom.:
18
Cov.:
31
AF XY:
0.000657
AC XY:
477
AN XY:
725994
show subpopulations
Gnomad4 AFR exome
AF:
0.000389
Gnomad4 AMR exome
AF:
0.000225
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0144
Gnomad4 SAS exome
AF:
0.00111
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000252
Gnomad4 OTH exome
AF:
0.00413
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00103
AC:
157
AN:
152296
Hom.:
2
Cov.:
31
AF XY:
0.00101
AC XY:
75
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.000481
Gnomad4 AMR
AF:
0.00124
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0195
Gnomad4 SAS
AF:
0.00249
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000384
Hom.:
0
Bravo
AF:
0.00148
Asia WGS
AF:
0.0180
AC:
63
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000594

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMay 17, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.50
Cadd
Benign
5.3
Dann
Benign
0.77

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs146460083; hg19: chr1-111858051; API