chr1-111318579-C-A

Variant names:

• chr1-111318579-C-A
• rs139093708
• NM_201653.4:c.816C>A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_201653.4(CHIA):​c.816C>A​(p.Ile272Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00535 in 1,614,194 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0055 (36 hom.)
• Consequence: CHIA NM_201653.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.121

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]

ENSG00000229283 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 1-111318579-C-A is Benign according to our data. Variant chr1-111318579-C-A is described in ClinVar as [Benign]. Clinvar id is 782080.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.121 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 36 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHIA	NM_201653.4	c.816C>A	p.Ile272Ile	synonymous_variant	Exon 9 of 12	ENST00000369740.6	NP_970615.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHIA	ENST00000369740.6	c.816C>A	p.Ile272Ile	synonymous_variant	Exon 9 of 12	1	NM_201653.4	ENSP00000358755.1

Frequencies

GnomAD3 genomes AF: 0.00388 AC: 590 AN: 152206 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000796

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00281

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0109

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00551

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00461 AC: 1159 AN: 251396 AF XY: 0.00456

Gnomad AFR exome AF: 0.000738

Gnomad AMR exome AF: 0.00237

Gnomad ASJ exome AF: 0.00258

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0116

Gnomad NFE exome AF: 0.00625

Gnomad OTH exome AF: 0.00587

GnomAD4 exome AF: 0.00551 AC: 8051 AN: 1461870 Hom.: 36 Cov.: 32 AF XY: 0.00531 AC XY: 3860 AN XY: 727234

Gnomad4 AFR exome AF: 0.000747 AC: 25 AN: 33480

Gnomad4 AMR exome AF: 0.00233 AC: 104 AN: 44724

Gnomad4 ASJ exome AF: 0.00187 AC: 49 AN: 26136

Gnomad4 EAS exome AF: 0.0000252 AC: 1 AN: 39700

Gnomad4 SAS exome AF: 0.00139 AC: 120 AN: 86256

Gnomad4 FIN exome AF: 0.0120 AC: 643 AN: 53420

Gnomad4 NFE exome AF: 0.00611 AC: 6797 AN: 1111994

Gnomad4 Remaining exome AF: 0.00510 AC: 308 AN: 60392

GnomAD4 genome AF: 0.00387 AC: 590 AN: 152324 Hom.: 0 Cov.: 32 AF XY: 0.00416 AC XY: 310 AN XY: 74472

Gnomad4 AFR AF: 0.000794 AC: 0.000793651 AN: 0.000793651

Gnomad4 AMR AF: 0.00281 AC: 0.00281082 AN: 0.00281082

Gnomad4 ASJ AF: 0.00259 AC: 0.00259217 AN: 0.00259217

Gnomad4 EAS AF: 0.000193 AC: 0.000193349 AN: 0.000193349

Gnomad4 SAS AF: 0.000622 AC: 0.000621633 AN: 0.000621633

Gnomad4 FIN AF: 0.0109 AC: 0.010929 AN: 0.010929

Gnomad4 NFE AF: 0.00551 AC: 0.00551114 AN: 0.00551114

Gnomad4 OTH AF: 0.00473 AC: 0.00473485 AN: 0.00473485

Alfa AF: 0.00485 Hom.: 1

Bravo AF: 0.00322

EpiCase AF: 0.00529

EpiControl AF: 0.00528

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 08, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	0.77
DANN	Benign	0.65
Mutation Taster		=100/0	polymorphism

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: rs139093708; hg19: chr1-111861201;