rs41272442

Positions:

• chr8-60830287-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.524

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD7	NM_017780.4	c.3523-35C>G		intron_variant		ENST00000423902.7	NP_060250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHD7	ENST00000423902.7	c.3523-35C>G		intron_variant		5	NM_017780.4	ENSP00000392028.1
CHD7	ENST00000524602.5	c.1717-31942C>G		intron_variant		1		ENSP00000437061.1
CHD7	ENST00000695853.1	n.3523-35C>G		intron_variant				ENSP00000512218.1

Frequencies

GnomAD3 genomes AF: 0.0578 AC: 8787 AN: 152086 Hom.: 694 Cov.: 32

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

GnomAD3 exomes AF: 0.0199 AC: 4476 AN: 224874 Hom.: 266 AF XY: 0.0173 AC XY: 2119 AN XY: 122386

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 SAS exome AF: 0.0146

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.: 30 AF XY: 0.0127 AC XY: 8952 AN XY: 707212

Gnomad4 AFR exome AF: 0.182

Gnomad4 AMR exome AF: 0.0142

Gnomad4 ASJ exome AF: 0.000691

Gnomad4 EAS exome AF: 0.00683

Gnomad4 SAS exome AF: 0.0141

Gnomad4 FIN exome AF: 0.00139

Gnomad4 NFE exome AF: 0.00876

Gnomad4 OTH exome AF: 0.0220

GnomAD4 genome AF: 0.0579 AC: 8820 AN: 152204 Hom.: 702 Cov.: 32 AF XY: 0.0567 AC XY: 4223 AN XY: 74432

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.0317

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00618

Gnomad4 SAS AF: 0.0143

Gnomad4 FIN AF: 0.00123

Gnomad4 NFE AF: 0.00816

Gnomad4 OTH AF: 0.0459

Alfa AF: 0.0288 Hom.: 53

Bravo AF: 0.0651

Asia WGS AF: 0.0360 AC: 123 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.1
DANN	Benign	0.73

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

LitVar

Other links and lift over

dbSNP: rs41272442; hg19: chr8-61742846;