8-60819983-CTT-CTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_017780.4(CHD7):c.2614-14dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00514 in 1,255,784 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000060 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0058 (0 hom.)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Not reported in ClinVar
• 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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.00583 (6448/1105466) while in subpopulation NFE AF= 0.00659 (5521/837966). AF 95% confidence interval is 0.00644. There are 0 homozygotes in gnomad4_exome. There are 2997 alleles in male gnomad4_exome subpopulation. Median coverage is 20. This position pass quality control queck.
• BS2: High AC in GnomAd at 9 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0000599 AC: 9 AN: 150318 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000489

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000890

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00583 AC: 6448 AN: 1105466 Hom.: 0 Cov.: 20 AF XY: 0.00543 AC XY: 2997 AN XY: 551594

Gnomad4 AFR exome AF: 0.00479

Gnomad4 AMR exome AF: 0.00331

Gnomad4 ASJ exome AF: 0.00296

Gnomad4 EAS exome AF: 0.00141

Gnomad4 SAS exome AF: 0.00442

Gnomad4 FIN exome AF: 0.00178

Gnomad4 NFE exome AF: 0.00659

Gnomad4 OTH exome AF: 0.00480

GnomAD4 genome AF: 0.0000599 AC: 9 AN: 150318 Hom.: 0 Cov.: 33 AF XY: 0.0000682 AC XY: 5 AN XY: 73280

Gnomad4 AFR AF: 0.0000489

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000890

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

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;