chr8-60819983-CT-C

Position:

• chr8-60819983-CT-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_017780.4(CHD7):​c.2614-14del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0223 in 1,268,764 control chromosomes in the GnomAD database, including 737 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (60 hom., cov: 33)
  • Exomes 𝑓: 0.023 (677 hom.)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.127

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 -16 ACMG points.

• BP6: Variant 8-60819983-CT-C is Benign according to our data. Variant chr8-60819983-CT-C is described in ClinVar as [Likely_benign]. Clinvar id is 210715.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-60819983-CT-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD7	NM_017780.4	c.2614-14del		intron_variant		ENST00000423902.7	NP_060250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHD7	ENST00000423902.7	c.2614-14del		intron_variant		5	NM_017780.4	ENSP00000392028	P1
CHD7	ENST00000524602.5	c.1716+38943del		intron_variant		1		ENSP00000437061
CHD7	ENST00000525508.1	c.2614-14del		intron_variant		5		ENSP00000436027
CHD7	ENST00000695853.1	c.2614-14del		intron_variant, NMD_transcript_variant				ENSP00000512218

Frequencies

GnomAD3 genomes AF: 0.0152 AC: 2283 AN: 150312 Hom.: 60 Cov.: 33

Gnomad AFR AF: 0.00335

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0194

Gnomad ASJ AF: 0.0293

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.0661

Gnomad FIN AF: 0.00542

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0102

Gnomad OTH AF: 0.0267

GnomAD4 exome AF: 0.0233 AC: 26014 AN: 1118342 Hom.: 677 Cov.: 20 AF XY: 0.0252 AC XY: 14028 AN XY: 557744

Gnomad4 AFR exome AF: 0.00836

Gnomad4 AMR exome AF: 0.0259

Gnomad4 ASJ exome AF: 0.0456

Gnomad4 EAS exome AF: 0.144

Gnomad4 SAS exome AF: 0.0809

Gnomad4 FIN exome AF: 0.00956

Gnomad4 NFE exome AF: 0.0139

Gnomad4 OTH exome AF: 0.0292

GnomAD4 genome AF: 0.0151 AC: 2275 AN: 150422 Hom.: 60 Cov.: 33 AF XY: 0.0166 AC XY: 1218 AN XY: 73402

Gnomad4 AFR AF: 0.00332

Gnomad4 AMR AF: 0.0194

Gnomad4 ASJ AF: 0.0293

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.0662

Gnomad4 FIN AF: 0.00542

Gnomad4 NFE AF: 0.0102

Gnomad4 OTH AF: 0.0279

Alfa AF: 0.0227 Hom.: 6

Bravo AF: 0.0145

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Jan 30, 2023	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Feb 07, 2019	- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 07, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs748282026; hg19: chr8-61732542;