8-60678764-C-CGCG

Position:

• chr8-60678764-C-CGCG

Variant summary

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

The NM_017780.4(CHD7):​c.-469_-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 0.65 (29156 hom., cov: 0)
  • Exomes 𝑓: 0.49 (54 hom.)
• Consequence: CHD7 NM_017780.4 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• 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 = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD7	NM_017780.4	c.-469_-467dup		5_prime_UTR_variant	1/38	ENST00000423902.7	NP_060250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHD7	ENST00000423902.7	c.-469_-467dup		5_prime_UTR_variant	1/38	5	NM_017780.4	ENSP00000392028	P1
CHD7	ENST00000695848.1	n.45_47dup		non_coding_transcript_exon_variant	1/7
CHD7	ENST00000695849.1	n.45_47dup		non_coding_transcript_exon_variant	1/7
CHD7	ENST00000695853.1	c.-469_-467dup		5_prime_UTR_variant, NMD_transcript_variant	1/37			ENSP00000512218

Frequencies

GnomAD3 genomes AF: 0.650 AC: 89392 AN: 137434 Hom.: 29162 Cov.: 0

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.733

Gnomad MID AF: 0.521

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.648

GnomAD4 exome AF: 0.493 AC: 299 AN: 606 Hom.: 54 Cov.: 0 AF XY: 0.503 AC XY: 174 AN XY: 346

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.750

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.563

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.351

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.650 AC: 89378 AN: 137426 Hom.: 29156 Cov.: 0 AF XY: 0.658 AC XY: 43859 AN XY: 66620

Gnomad4 AFR AF: 0.655

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.644

Gnomad4 EAS AF: 0.693

Gnomad4 SAS AF: 0.692

Gnomad4 FIN AF: 0.733

Gnomad4 NFE AF: 0.629

Gnomad4 OTH AF: 0.649

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

CHARGE syndrome Uncertain:1

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

-

- -

Hypogonadism with anosmia Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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;