8-60678764-C-CGCGGCG

Position:

• chr8-60678764-C-CGCGGCG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_017780.4(CHD7):​c.-472_-467dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.092 (801 hom., cov: 0)
  • Exomes 𝑓: 0.069 (3 hom.)
• Consequence: CHD7 NM_017780.4 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:5
• Conservation: PhyloP100: 0.400

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.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHD7	NM_017780.4	c.-472_-467dup		5_prime_UTR_variant	1/38	ENST00000423902.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHD7	ENST00000423902.7	c.-472_-467dup		5_prime_UTR_variant	1/38	5	NM_017780.4	P1
CHD7	ENST00000695848.1	n.42_47dup		non_coding_transcript_exon_variant	1/7
CHD7	ENST00000695849.1	n.42_47dup		non_coding_transcript_exon_variant	1/7
CHD7	ENST00000695853.1	c.-472_-467dup		5_prime_UTR_variant, NMD_transcript_variant	1/37

Frequencies

GnomAD3 genomes AF: 0.0921 AC: 12663 AN: 137510 Hom.: 801 Cov.: 0

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.0401

Gnomad AMR AF: 0.0550

Gnomad ASJ AF: 0.0675

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0464

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.0699

Gnomad OTH AF: 0.0734

GnomAD4 exome AF: 0.0686 AC: 42 AN: 612 Hom.: 3 Cov.: 0 AF XY: 0.0514 AC XY: 18 AN XY: 350

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0850

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0361

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.0921 AC: 12665 AN: 137504 Hom.: 801 Cov.: 0 AF XY: 0.0913 AC XY: 6085 AN XY: 66660

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.0549

Gnomad4 ASJ AF: 0.0675

Gnomad4 EAS AF: 0.197

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.0464

Gnomad4 NFE AF: 0.0699

Gnomad4 OTH AF: 0.0745

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

CHARGE syndrome Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

Hypogonadism with anosmia Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

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- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs886063023; hg19: chr8-61591323;