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GeneBe

1-6106769-C-T

Variant summary

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

The NM_015557.3(CHD5):c.5589G>A(p.Gln1863=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000378 in 1,595,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00039 ( 0 hom. )

Consequence

CHD5
NM_015557.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.53
Variant links:
Genes affected
CHD5 (HGNC:16816): (chromodomain helicase DNA binding protein 5) This gene encodes a member of the chromodomain helicase DNA-binding protein family. Members of this family are characterized by a chromodomain, a helicase ATP-binding domain and an additional functional domain. This gene encodes a neuron-specific protein that may function in chromatin remodeling and gene transcription. This gene is a potential tumor suppressor gene that may play a role in the development of neuroblastoma. [provided by RefSeq, Feb 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 1-6106769-C-T is Benign according to our data. Variant chr1-6106769-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 729293.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=2.53 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000274 (41/149670) while in subpopulation AMR AF= 0.000333 (5/15020). AF 95% confidence interval is 0.000196. There are 0 homozygotes in gnomad4. There are 19 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 AC in GnomAd at 41 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CHD5NM_015557.3 linkuse as main transcriptc.5589G>A p.Gln1863= synonymous_variant 39/42 ENST00000262450.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CHD5ENST00000262450.8 linkuse as main transcriptc.5589G>A p.Gln1863= synonymous_variant 39/421 NM_015557.3 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000274
AC:
41
AN:
149556
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000494
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000333
Gnomad ASJ
AF:
0.00347
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000214
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000296
Gnomad OTH
AF:
0.000487
GnomAD3 exomes
AF:
0.000569
AC:
140
AN:
245856
Hom.:
0
AF XY:
0.000673
AC XY:
90
AN XY:
133794
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000552
Gnomad ASJ exome
AF:
0.00487
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000854
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000373
Gnomad OTH exome
AF:
0.00100
GnomAD4 exome
AF:
0.000389
AC:
562
AN:
1445546
Hom.:
0
Cov.:
34
AF XY:
0.000431
AC XY:
310
AN XY:
718874
show subpopulations
Gnomad4 AFR exome
AF:
0.0000605
Gnomad4 AMR exome
AF:
0.000611
Gnomad4 ASJ exome
AF:
0.00533
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000966
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000210
Gnomad4 OTH exome
AF:
0.00111
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000274
AC:
41
AN:
149670
Hom.:
0
Cov.:
32
AF XY:
0.000261
AC XY:
19
AN XY:
72904
show subpopulations
Gnomad4 AFR
AF:
0.0000493
Gnomad4 AMR
AF:
0.000333
Gnomad4 ASJ
AF:
0.00347
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000215
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000296
Gnomad4 OTH
AF:
0.000482
Alfa
AF:
0.000641
Hom.:
0
Bravo
AF:
0.000404
EpiCase
AF:
0.000436
EpiControl
AF:
0.000534

ClinVar

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

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeMay 30, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.50
Cadd
Benign
8.0
Dann
Benign
0.87

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: rs147871474; hg19: chr1-6166829; API