5-98856627-G-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2

The NM_001270.4(CHD1):ā€‹c.4886C>Gā€‹(p.Ser1629Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000291 in 1,613,090 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000033 ( 0 hom., cov: 32)
Exomes š‘“: 0.000029 ( 0 hom. )

Consequence

CHD1
NM_001270.4 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.78
Variant links:
Genes affected
CHD1 (HGNC:1915): (chromodomain helicase DNA binding protein 1) The CHD family of proteins is characterized by the presence of chromo (chromatin organization modifier) domains and SNF2-related helicase/ATPase domains. CHD genes alter gene expression possibly by modification of chromatin structure thus altering access of the transcriptional apparatus to its chromosomal DNA template. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.20279568).
BS1
Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0000287 (42/1460978) while in subpopulation NFE AF= 0.0000369 (41/1111274). AF 95% confidence interval is 0.0000274. There are 0 homozygotes in gnomad4_exome. There are 24 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CHD1NM_001270.4 linkc.4886C>G p.Ser1629Cys missense_variant 36/36 ENST00000614616.5 NP_001261.2 O14646-1B3KT33

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CHD1ENST00000614616.5 linkc.4886C>G p.Ser1629Cys missense_variant 36/365 NM_001270.4 ENSP00000483667.1 O14646-1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152112
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000943
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251068
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135694
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000287
AC:
42
AN:
1460978
Hom.:
0
Cov.:
32
AF XY:
0.0000330
AC XY:
24
AN XY:
726836
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.0000369
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152112
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74320
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000943
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000564
Hom.:
0
Bravo
AF:
0.0000189
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.0000546
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

Pilarowski-Bjornsson syndrome Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInstitute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital BonnAug 17, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.082
BayesDel_addAF
Benign
-0.058
T
BayesDel_noAF
Benign
-0.21
CADD
Uncertain
24
DANN
Benign
0.92
DEOGEN2
Benign
0.099
T;T
Eigen
Benign
0.13
Eigen_PC
Uncertain
0.30
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.89
.;D
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.20
T;T
MetaSVM
Uncertain
0.037
D
MutationAssessor
Uncertain
2.3
M;M
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-1.8
.;N
REVEL
Benign
0.25
Sift
Benign
0.059
.;T
Sift4G
Uncertain
0.042
D;D
Polyphen
0.21
B;B
Vest4
0.28
MVP
0.79
MPC
0.043
ClinPred
0.37
T
GERP RS
5.5
Varity_R
0.091
gMVP
0.45

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: rs767095541; hg19: chr5-98192331; API