dbSNP rs41272442: CHD7:c.3523-35C>G (chr8-60830287-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017780.4(CHD7):c.3523-35C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0175 in 1,577,700 control chromosomes in the GnomAD database, including 1,345 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.058 ( 702 hom., cov: 32)

Exomes 𝑓: 0.013 ( 643 hom. )

Consequence

CHD7
NM_017780.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.524

Publications

5 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: Orphanet, G2P, Labcorp Genetics (formerly Invitae), Broad Center for Mendelian Genomics, ClinGen
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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 8-60830287-C-G is Benign according to our data. Variant chr8-60830287-C-G is described in ClinVar as Benign. ClinVar VariationId is 260903.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

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.3523-35C>G		intron	N/A	NP_060250.2
	CHD7	NM_001316690.1		c.1717-31942C>G		intron	N/A	NP_001303619.1	Q9P2D1-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHD7	ENST00000423902.7	TSL:5 MANE Select	c.3523-35C>G	intron	N/A	ENSP00000392028.1	Q9P2D1-1
CHD7	ENST00000524602.5	TSL:1	c.1717-31942C>G	intron	N/A	ENSP00000437061.1	Q9P2D1-4
CHD7	ENST00000933299.1		c.3523-35C>G	intron	N/A	ENSP00000603358.1

Frequencies

GnomAD3 genomes

AF:

0.0578

AC:

8787

AN:

152086

Hom.:

694

Cov.:

show subpopulations

Gnomad AFR

AF:

0.182

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0318

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00636

Gnomad SAS

AF:

0.0151

Gnomad FIN

AF:

0.00123

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00816

Gnomad OTH

AF:

0.0435

GnomAD2 exomes

AF:

0.0199

AC:

4476

AN:

224874

AF XY:

0.0173

show subpopulations

Gnomad AFR exome

AF:

0.183

Gnomad AMR exome

AF:

0.0128

Gnomad ASJ exome

AF:

0.000478

Gnomad EAS exome

AF:

0.00694

Gnomad FIN exome

AF:

0.00121

Gnomad NFE exome

AF:

0.00805

Gnomad OTH exome

AF:

0.0126

GnomAD4 exome

AF:

0.0131

AC:

18714

AN:

1425496

Hom.:

643

Cov.:

AF XY:

0.0127

AC XY:

8952

AN XY:

707212

show subpopulations

African (AFR)

AF:

0.182

AC:

5708

AN:

31310

American (AMR)

AF:

0.0142

AC:

537

AN:

37864

Ashkenazi Jewish (ASJ)

AF:

0.000691

AC:

AN:

24614

East Asian (EAS)

AF:

0.00683

AC:

269

AN:

39382

South Asian (SAS)

AF:

0.0141

AC:

1136

AN:

80588

European-Finnish (FIN)

AF:

0.00139

AC:

AN:

52548

Middle Eastern (MID)

AF:

0.0176

AC:

AN:

5466

European-Non Finnish (NFE)

AF:

0.00876

AC:

9588

AN:

1095034

Other (OTH)

AF:

0.0220

AC:

1290

AN:

58690

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

701

1401

2102

2802

3503

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

490

980

1470

1960

2450

<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:

0.0579

AC:

8820

AN:

152204

Hom.:

702

Cov.:

AF XY:

0.0567

AC XY:

4223

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.182

AC:

7563

AN:

41498

American (AMR)

AF:

0.0317

AC:

485

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.000864

AC:

AN:

3472

East Asian (EAS)

AF:

0.00618

AC:

AN:

5178

South Asian (SAS)

AF:

0.0143

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00123

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00816

AC:

555

AN:

68022

Other (OTH)

AF:

0.0459

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

377

754

1131

1508

1885

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

258

344

430

<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:

0.0288

Hom.:

Bravo

AF:

0.0651

Asia WGS

AF:

0.0360

AC:

123

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

8.1

(source)

DANN

Benign

0.73

PhyloP100

0.52

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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