chr8-60854511-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS1

The NM_017780.4(CHD7):c.6924G>A(p.Ser2308Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00031 in 1,598,904 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. S2308S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

CHD7
NM_017780.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.896

Publications

1 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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 8-60854511-G-A is Benign according to our data. Variant chr8-60854511-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 363476.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.896 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00137 (209/152336) while in subpopulation AFR AF = 0.00462 (192/41574). AF 95% confidence interval is 0.00408. There are 1 homozygotes in GnomAd4. There are 106 alleles in the male GnomAd4 subpopulation. Median coverage is 33. 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD7	NM_017780.4	MANE Select	c.6924G>A	p.Ser2308Ser	synonymous	Exon 32 of 38	NP_060250.2
	CHD7	NM_001316690.1		c.1717-7718G>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.6924G>A	p.Ser2308Ser	synonymous	Exon 32 of 38	ENSP00000392028.1
CHD7	ENST00000524602.5	TSL:1	c.1717-7718G>A		intron	N/A	ENSP00000437061.1
CHD7	ENST00000933299.1		c.6957G>A	p.Ser2319Ser	synonymous	Exon 32 of 38	ENSP00000603358.1

Frequencies

GnomAD3 genomes

AF:

0.00137

AC:

209

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00463

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.000411

AC:

101

AN:

245680

AF XY:

0.000360

show subpopulations

Gnomad AFR exome

AF:

0.00492

Gnomad AMR exome

AF:

0.000473

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000627

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000198

AC:

286

AN:

1446568

Hom.:

Cov.:

AF XY:

0.000193

AC XY:

138

AN XY:

716690

show subpopulations

African (AFR)

AF:

0.00602

AC:

200

AN:

33200

American (AMR)

AF:

0.000613

AC:

AN:

44076

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25818

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39320

South Asian (SAS)

AF:

0.0000588

AC:

AN:

85014

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53176

Middle Eastern (MID)

AF:

0.000524

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

0.0000318

AC:

AN:

1100480

Other (OTH)

AF:

0.000251

AC:

AN:

59756

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

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:

0.00137

AC:

209

AN:

152336

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

106

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.00462

AC:

192

AN:

41574

American (AMR)

AF:

0.000392

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68028

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000278

Hom.:

Bravo

AF:

0.00163

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

CHARGE syndrome (1)

CHARGE syndrome;C3552553:Hypogonadotropic hypogonadism 5 with or without anosmia (1)

Hypogonadotropic hypogonadism 5 with or without anosmia (1)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

0.33

(source)

DANN

Benign

0.82

PhyloP100

-0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over