rs41312172

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_017780.4(CHD7):​c.6282A>G​(p.Gly2094Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00668 in 1,613,962 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0047 ( 5 hom., cov: 32)
Exomes 𝑓: 0.0069 ( 31 hom. )

Consequence

CHD7
NM_017780.4 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: -0.808
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 -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 8-60853007-A-G is Benign according to our data. Variant chr8-60853007-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 95803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-60853007-A-G is described in Lovd as [Likely_benign]. Variant chr8-60853007-A-G is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-0.808 with no splicing effect.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00466 (710/152250) while in subpopulation AMR AF= 0.00916 (140/15290). AF 95% confidence interval is 0.00792. There are 5 homozygotes in gnomad4. There are 342 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 710 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CHD7NM_017780.4 linkc.6282A>G p.Gly2094Gly synonymous_variant Exon 31 of 38 ENST00000423902.7 NP_060250.2 Q9P2D1-1Q6ZWF9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CHD7ENST00000423902.7 linkc.6282A>G p.Gly2094Gly synonymous_variant Exon 31 of 38 5 NM_017780.4 ENSP00000392028.1 Q9P2D1-1
CHD7ENST00000524602.5 linkc.1717-9222A>G intron_variant Intron 2 of 4 1 ENSP00000437061.1 Q9P2D1-4
CHD7ENST00000695853.1 linkn.6282A>G non_coding_transcript_exon_variant Exon 31 of 37 ENSP00000512218.1 A0A8Q3WKT9

Frequencies

GnomAD3 genomes
AF:
0.00467
AC:
710
AN:
152132
Hom.:
5
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00118
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00917
Gnomad ASJ
AF:
0.000577
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00187
Gnomad FIN
AF:
0.00122
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00719
Gnomad OTH
AF:
0.00382
GnomAD3 exomes
AF:
0.00436
AC:
1087
AN:
249154
Hom.:
4
AF XY:
0.00456
AC XY:
617
AN XY:
135170
show subpopulations
Gnomad AFR exome
AF:
0.00129
Gnomad AMR exome
AF:
0.00336
Gnomad ASJ exome
AF:
0.000298
Gnomad EAS exome
AF:
0.0000556
Gnomad SAS exome
AF:
0.00212
Gnomad FIN exome
AF:
0.00149
Gnomad NFE exome
AF:
0.00732
Gnomad OTH exome
AF:
0.00397
GnomAD4 exome
AF:
0.00689
AC:
10066
AN:
1461712
Hom.:
31
Cov.:
32
AF XY:
0.00676
AC XY:
4917
AN XY:
727138
show subpopulations
Gnomad4 AFR exome
AF:
0.000896
Gnomad4 AMR exome
AF:
0.00311
Gnomad4 ASJ exome
AF:
0.000574
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00211
Gnomad4 FIN exome
AF:
0.00148
Gnomad4 NFE exome
AF:
0.00827
Gnomad4 OTH exome
AF:
0.00704
GnomAD4 genome
AF:
0.00466
AC:
710
AN:
152250
Hom.:
5
Cov.:
32
AF XY:
0.00459
AC XY:
342
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.00118
Gnomad4 AMR
AF:
0.00916
Gnomad4 ASJ
AF:
0.000577
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00187
Gnomad4 FIN
AF:
0.00122
Gnomad4 NFE
AF:
0.00719
Gnomad4 OTH
AF:
0.00378
Alfa
AF:
0.00511
Hom.:
3
Bravo
AF:
0.00478
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.00791
EpiControl
AF:
0.00699

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:14
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:7
Feb 11, 2015
Eurofins Ntd Llc (ga)
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Aug 23, 2017
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

p.Gly2094Gly in exon 31 of CHD7: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 0.65% (432/66718) o f European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.br oadinstitute.org; dbSNP rs41312172). -

-
Clinical Genetics, Academic Medical Center
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

-
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Feb 08, 2013
Genetic Services Laboratory, University of Chicago
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

May 03, 2017
Athena Diagnostics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not provided Benign:3
-
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Mar 01, 2025
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

CHD7: BP4, BP7, BS2 -

Mar 03, 2015
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

CHARGE syndrome Benign:1
Jan 31, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Inborn genetic diseases Benign:1
Sep 09, 2015
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

CHARGE syndrome;C3552553:Hypogonadotropic hypogonadism 5 with or without anosmia Benign:1
Jul 26, 2021
Fulgent Genetics, Fulgent Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Hypogonadotropic hypogonadism 5 with or without anosmia Benign:1
Apr 27, 2017
Illumina Laboratory Services, Illumina
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
1.3
DANN
Benign
0.52
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.2

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: rs41312172; hg19: chr8-61765566; API