rs1187193827

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2

The NM_017780.4(CHD7):​c.2062G>A​(p.Ala688Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000393 in 1,525,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

CHD7
NM_017780.4 missense

Scores

1
18

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.666
Variant links:
Genes affected
CHD7 (HGNC:20626): (chromodomain helicase DNA binding protein 7) This gene encodes a protein that contains several helicase family domains. Mutations in this gene have been found in some patients with the CHARGE syndrome. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), CHD7. . Gene score misZ 3.2193 (greater than the threshold 3.09). Trascript score misZ 3.9401 (greater than threshold 3.09). GenCC has associacion of gene with Kallmann syndrome, hypogonadotropic hypogonadism 5 with or without anosmia, CHARGE syndrome, hypogonadotropic hypogonadism, Omenn syndrome.
BP4
Computational evidence support a benign effect (MetaRNN=0.04325211).
BP6
Variant 8-60781396-G-A is Benign according to our data. Variant chr8-60781396-G-A is described in ClinVar as [Benign]. Clinvar id is 529118.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CHD7NM_017780.4 linkuse as main transcriptc.2062G>A p.Ala688Thr missense_variant 3/38 ENST00000423902.7 NP_060250.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CHD7ENST00000423902.7 linkuse as main transcriptc.2062G>A p.Ala688Thr missense_variant 3/385 NM_017780.4 ENSP00000392028 P1Q9P2D1-1

Frequencies

GnomAD3 genomes
AF:
0.00000660
AC:
1
AN:
151594
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
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:
0.00
GnomAD3 exomes
AF:
0.0000202
AC:
3
AN:
148280
Hom.:
0
AF XY:
0.0000126
AC XY:
1
AN XY:
79630
show subpopulations
Gnomad AFR exome
AF:
0.000324
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:
0.00
GnomAD4 exome
AF:
0.00000364
AC:
5
AN:
1374006
Hom.:
0
Cov.:
32
AF XY:
0.00000147
AC XY:
1
AN XY:
678670
show subpopulations
Gnomad4 AFR exome
AF:
0.000170
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000660
AC:
1
AN:
151594
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74040
show subpopulations
Gnomad4 AFR
AF:
0.0000242
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:
0.00
Alfa
AF:
0.0000335
Hom.:
0
Bravo
AF:
0.0000302

ClinVar

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

Submissions by phenotype

CHARGE syndrome Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.060
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.064
T;.
Eigen
Benign
-0.54
Eigen_PC
Benign
-0.34
FATHMM_MKL
Benign
0.75
D
LIST_S2
Benign
0.70
T;T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.043
T;T
MetaSVM
Benign
-0.89
T
MutationAssessor
Benign
-1.0
N;N
MutationTaster
Benign
1.0
D;N;N;N
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-0.42
N;N
REVEL
Benign
0.16
Sift
Benign
0.73
T;T
Sift4G
Benign
0.58
T;T
Polyphen
0.0
B;.
Vest4
0.12
MVP
0.63
MPC
0.26
ClinPred
0.099
T
GERP RS
2.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.035
gMVP
0.11

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: rs1187193827; hg19: chr8-61693955; API