8-60820073-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_017780.4(CHD7):c.2680A>G(p.Thr894Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00166 in 1,608,816 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 65 hom. )

Consequence

CHD7
NM_017780.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 5.03

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]

CHD7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00936836).

BP6

Variant 8-60820073-A-G is Benign according to our data. Variant chr8-60820073-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 199142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-60820073-A-G is described in Lovd as [Likely_benign]. Variant chr8-60820073-A-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0011 (168/152172) while in subpopulation SAS AF= 0.0332 (160/4818). AF 95% confidence interval is 0.029. There are 1 homozygotes in gnomad4. There are 123 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 168 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD7	NM_017780.4 link	c.2680A>G	p.Thr894Ala	missense_variant	Exon 9 of 38	ENST00000423902.7	NP_060250.2	Q9P2D1-1Q6ZWF9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHD7	ENST00000423902.7 link	c.2680A>G	p.Thr894Ala	missense_variant	Exon 9 of 38	5	NM_017780.4	ENSP00000392028.1	Q9P2D1-1
CHD7	ENST00000524602.5 link	c.1716+39023A>G		intron_variant	Intron 2 of 4	1		ENSP00000437061.1	Q9P2D1-4
CHD7	ENST00000525508.1 link	c.2680A>G	p.Thr894Ala	missense_variant	Exon 8 of 12	5		ENSP00000436027.1	Q9P2D1-2
CHD7	ENST00000695853.1 link	n.2680A>G		non_coding_transcript_exon_variant	Exon 9 of 37			ENSP00000512218.1	A0A8Q3WKT9

Frequencies

GnomAD3 genomes

AF:

0.00112

AC:

170

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0336

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00329

AC:

799

AN:

243200

Hom.:

AF XY:

0.00455

AC XY:

599

AN XY:

131564

show subpopulations

Gnomad AFR exome

AF:

0.000267

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000227

Gnomad SAS exome

AF:

0.0264

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000454

Gnomad OTH exome

AF:

0.00236

GnomAD4 exome

AF:

0.00172

AC:

2510

AN:

1456644

Hom.:

Cov.:

AF XY:

0.00252

AC XY:

1824

AN XY:

724260

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.0278

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000171

Gnomad4 OTH exome

AF:

0.00188

GnomAD4 genome

AF:

0.00110

AC:

168

AN:

152172

Hom.:

Cov.:

AF XY:

0.00165

AC XY:

123

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0332

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000283

Hom.:

Bravo

AF:

0.000185

ESP6500AA

AF:

0.000263

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00385

AC:

465

Asia WGS

AF:

0.0100

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

May 13, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Feb 09, 2017

Eurofins Ntd Llc (ga)

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.Thr894Ala in exon 9 of CHD7: This variant is not expected to have clinical sig nificance because it has been identified in 3.48% (412/11846) of South Asian chr omosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.o rg; dbSNP rs377662366). -

CHARGE syndrome

Benign:1

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases

Benign:1

Nov 18, 2016

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as 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. -

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

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.33

T;.

Eigen

Benign

0.13

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.71

T;T

MetaRNN

Benign

0.0094

T;T

MetaSVM

Benign

-0.54

MutationAssessor

Uncertain

2.6

M;M

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.23

Sift

Benign

0.30

T;T

Sift4G

Benign

0.51

T;T

Polyphen

0.13

B;B

Vest4

0.53

MVP

0.85

MPC

0.16

ClinPred

0.031

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.17

gMVP

0.41

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over