Variant 11-893472-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_023947.4(CHID1):c.656C>T(p.Ala219Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000284 in 1,551,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

CHID1
NM_023947.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.49

Variant links:

Genes affected

CHID1 (HGNC:28474): (chitinase domain containing 1) Enables oligosaccharide binding activity. Involved in negative regulation of cytokine production involved in inflammatory response. Located in several cellular components, including late endosome; lysosome; and trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

CHID1 links:

CHID1 (HGNC:):

CHID1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14451069).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHID1	NM_023947.4 linkuse as main transcript	c.656C>T	p.Ala219Val	missense_variant	8/13	ENST00000323578.13	NP_076436.3	Q9BWS9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHID1	ENST00000323578.13 linkuse as main transcript	c.656C>T	p.Ala219Val	missense_variant	8/13	1	NM_023947.4	ENSP00000325055.8		Q9BWS9-1

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000253

AC:

AN:

157978

Hom.:

AF XY:

0.0000361

AC XY:

AN XY:

83128

show subpopulations

Gnomad AFR exome

AF:

0.000330

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000227

GnomAD4 exome

AF:

0.0000229

AC:

AN:

1399530

Hom.:

Cov.:

AF XY:

0.0000246

AC XY:

AN XY:

690380

show subpopulations

Gnomad4 AFR exome

AF:

0.000721

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000371

Gnomad4 OTH exome

AF:

0.0000345

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000574

Hom.:

Bravo

AF:

0.000144

ESP6500AA

AF:

0.000239

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000108

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 18, 2022

The c.731C>T (p.A244V) alteration is located in exon 9 (coding exon 8) of the CHID1 gene. This alteration results from a C to T substitution at nucleotide position 731, causing the alanine (A) at amino acid position 244 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.0080

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.059

.;T;T;.;T;T

Eigen

Benign

0.18

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.73

T;T;.;.;.;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.14

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

.;L;L;.;L;.

MutationTaster

Benign

0.92

D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-2.1

N;N;N;N;N;N

REVEL

Benign

0.16

Sift

Benign

0.13

T;T;T;T;T;T

Sift4G

Benign

0.21

T;T;T;T;T;.

Polyphen

0.84

P;P;P;P;P;.

Vest4

0.25

MVP

0.27

MPC

0.28

ClinPred

0.20

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.61

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over