5-98856391-G-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2

The NM_001270.4(CHD1):​c.5122C>T​(p.Arg1708Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000192 in 1,606,840 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

CHD1
NM_001270.4 missense

Scores

3
12
4

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 7.18
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 Likely_benign. Variant got -3 ACMG points.

PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), CHD1. . Trascript score misZ 3.2778 (greater than threshold 3.09). GenCC has associacion of gene with Pilarowski-Bjornsson syndrome.
BS2
High AC in GnomAd4 at 32 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CHD1NM_001270.4 linkuse as main transcriptc.5122C>T p.Arg1708Trp missense_variant 36/36 ENST00000614616.5 NP_001261.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CHD1ENST00000614616.5 linkuse as main transcriptc.5122C>T p.Arg1708Trp missense_variant 36/365 NM_001270.4 ENSP00000483667 P2O14646-1

Frequencies

GnomAD3 genomes
AF:
0.000210
AC:
32
AN:
152024
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000966
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000918
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:
0.000206
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000184
AC:
46
AN:
250424
Hom.:
0
AF XY:
0.000214
AC XY:
29
AN XY:
135404
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000203
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000928
Gnomad NFE exome
AF:
0.000318
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000190
AC:
277
AN:
1454816
Hom.:
0
Cov.:
30
AF XY:
0.000201
AC XY:
145
AN XY:
722496
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000135
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0000375
Gnomad4 NFE exome
AF:
0.000238
Gnomad4 OTH exome
AF:
0.0000666
GnomAD4 genome
AF:
0.000210
AC:
32
AN:
152024
Hom.:
0
Cov.:
32
AF XY:
0.000229
AC XY:
17
AN XY:
74254
show subpopulations
Gnomad4 AFR
AF:
0.0000966
Gnomad4 AMR
AF:
0.000918
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000206
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000203
Hom.:
0
Bravo
AF:
0.000196
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000189
AC:
23
EpiCase
AF:
0.000273
EpiControl
AF:
0.000296

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 21, 2021The c.5122C>T (p.R1708W) alteration is located in exon 35 (coding exon 35) of the CHD1 gene. This alteration results from a C to T substitution at nucleotide position 5122, causing the arginine (R) at amino acid position 1708 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingClinical Genetics Laboratory, Skane University Hospital LundSep 21, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.70
BayesDel_addAF
Uncertain
0.080
D
BayesDel_noAF
Pathogenic
0.18
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.097
T;T
Eigen
Uncertain
0.65
Eigen_PC
Uncertain
0.62
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.93
.;D
M_CAP
Benign
0.084
D
MetaRNN
Uncertain
0.55
D;D
MetaSVM
Uncertain
0.77
D
MutationAssessor
Uncertain
2.6
M;M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.70
T
PROVEAN
Uncertain
-2.8
.;D
REVEL
Uncertain
0.63
Sift
Uncertain
0.026
.;D
Sift4G
Benign
0.073
T;T
Polyphen
1.0
D;D
Vest4
0.67
MVP
0.78
MPC
0.13
ClinPred
0.37
T
GERP RS
4.6
Varity_R
0.17
gMVP
0.67

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: rs200109773; hg19: chr5-98192095; COSMIC: COSV99399560; COSMIC: COSV99399560; API