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GeneBe

3-53822641-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_018397.5(CHDH):c.705C>T(p.Gly235=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00185 in 1,607,334 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0097 ( 27 hom., cov: 32)
Exomes 𝑓: 0.0010 ( 31 hom. )

Consequence

CHDH
NM_018397.5 splice_region, synonymous

Scores

2
Splicing: ADA: 0.003007
2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.65
Variant links:
Genes affected
CHDH (HGNC:24288): (choline dehydrogenase) The protein encoded by this gene is a choline dehydrogenase that localizes to the mitochondrion. Variations in this gene can affect susceptibility to choline deficiency. A few transcript variants have been found for this gene, but the full-length nature of only one has been characterized to date. [provided by RefSeq, Dec 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 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=-0.39).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-53822641-G-A is Benign according to our data. Variant chr3-53822641-G-A is described in ClinVar as [Benign]. Clinvar id is 767915.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=1.65 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00974 (1484/152372) while in subpopulation AFR AF= 0.0341 (1416/41578). AF 95% confidence interval is 0.0326. There are 27 homozygotes in gnomad4. There are 681 alleles in male gnomad4 subpopulation. Median coverage is 32. 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 27 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CHDHNM_018397.5 linkuse as main transcriptc.705C>T p.Gly235= splice_region_variant, synonymous_variant 4/9 ENST00000315251.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CHDHENST00000315251.11 linkuse as main transcriptc.705C>T p.Gly235= splice_region_variant, synonymous_variant 4/91 NM_018397.5 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00973
AC:
1482
AN:
152254
Hom.:
27
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0341
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00340
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:
0.0000441
Gnomad OTH
AF:
0.00621
GnomAD3 exomes
AF:
0.00237
AC:
582
AN:
246076
Hom.:
12
AF XY:
0.00158
AC XY:
211
AN XY:
133482
show subpopulations
Gnomad AFR exome
AF:
0.0308
Gnomad AMR exome
AF:
0.00154
Gnomad ASJ exome
AF:
0.0000998
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000124
Gnomad OTH exome
AF:
0.00230
GnomAD4 exome
AF:
0.00102
AC:
1490
AN:
1454962
Hom.:
31
Cov.:
33
AF XY:
0.000879
AC XY:
636
AN XY:
723840
show subpopulations
Gnomad4 AFR exome
AF:
0.0355
Gnomad4 AMR exome
AF:
0.00215
Gnomad4 ASJ exome
AF:
0.0000766
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000468
Gnomad4 OTH exome
AF:
0.00227
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00974
AC:
1484
AN:
152372
Hom.:
27
Cov.:
32
AF XY:
0.00914
AC XY:
681
AN XY:
74512
show subpopulations
Gnomad4 AFR
AF:
0.0341
Gnomad4 AMR
AF:
0.00340
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00614
Alfa
AF:
0.00220
Hom.:
5
Bravo
AF:
0.0112
Asia WGS
AF:
0.00202
AC:
7
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.0000593

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 testingInvitaeMar 02, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.39
Cadd
Benign
13
Dann
Benign
0.77
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.6

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.0030
dbscSNV1_RF
Benign
0.020
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: rs7641850; hg19: chr3-53856668; API