rs1187193827

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1

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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A688V) has been classified as Benign.

Frequency

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

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

CHD7
NM_017780.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.666

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

CHARGE syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, Broad Center for Mendelian Genomics, ClinGen, G2P
hypogonadotropic hypogonadism 5 with or without anosmia
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
hypogonadotropic hypogonadism
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Kallmann syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Omenn syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CHD7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

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 VariationId is 529118.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.00000364 (5/1374006) while in subpopulation AFR AF = 0.00017 (5/29462). AF 95% confidence interval is 0.0000659. There are 0 homozygotes in GnomAdExome4. There are 1 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017780.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD7	NM_017780.4	MANE Select	c.2062G>A	p.Ala688Thr	missense	Exon 3 of 38	NP_060250.2
	CHD7	NM_001316690.1		c.1716+346G>A		intron	N/A	NP_001303619.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CHD7	ENST00000423902.7	TSL:5 MANE Select	c.2062G>A	p.Ala688Thr	missense	Exon 3 of 38	ENSP00000392028.1
CHD7	ENST00000524602.5	TSL:1	c.1716+346G>A		intron	N/A	ENSP00000437061.1
CHD7	ENST00000525508.1	TSL:5	c.2062G>A	p.Ala688Thr	missense	Exon 2 of 12	ENSP00000436027.1

Frequencies

GnomAD3 genomes

AF:

0.00000660

AC:

AN:

151594

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.0000202

AC:

AN:

148280

AF XY:

0.0000126

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000364

AC:

AN:

1374006

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

678670

show subpopulations

African (AFR)

AF:

0.000170

AC:

AN:

29462

American (AMR)

AF:

0.00

AC:

AN:

26010

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23114

East Asian (EAS)

AF:

0.00

AC:

AN:

36784

South Asian (SAS)

AF:

0.00

AC:

AN:

72492

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49510

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5490

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1074174

Other (OTH)

AF:

0.00

AC:

AN:

56970

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000660

AC:

AN:

151594

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74040

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41374

American (AMR)

AF:

0.00

AC:

AN:

15216

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10562

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67670

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000335

Hom.:

Bravo

AF:

0.0000302

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

CHARGE syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.064

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.70

M_CAP

Benign

0.018

MetaRNN

Benign

0.043

MetaSVM

Benign

-0.89

MutationAssessor

Benign

-1.0

PhyloP100

0.67

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.42

REVEL

Benign

0.16

Sift

Benign

0.73

Sift4G

Benign

0.58

Polyphen

0.0

Vest4

0.12

MVP

0.63

MPC

0.26

ClinPred

0.099

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.035

gMVP

0.11

Mutation Taster

=83/17

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over