rs5891777

Variant names:

• chr8-60800567-A-ATGGACT
• rs5891777
• NM_017780.4:c.2376+43_2376+48dupTGGACT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_017780.4(CHD7):​c.2376+43_2376+48dupTGGACT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.776 in 1,550,796 control chromosomes in the GnomAD database, including 469,561 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (45749 hom., cov: 0)
  • Exomes 𝑓: 0.78 (423812 hom.)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.541
• Publications: 5 publications found

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]

CHD7 Gene-Disease associations (from GenCC):

• CHARGE syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, Broad Center for Mendelian Genomics, ClinGen, G2P
• hypogonadotropic hypogonadism 5 with or without anosmia

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• hypogonadotropic hypogonadism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Kallmann syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Omenn syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 8-60800567-A-ATGGACT is Benign according to our data. Variant chr8-60800567-A-ATGGACT is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260894.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD7	NM_017780.4	c.2376+43_2376+48dupTGGACT		intron_variant	Intron 5 of 37	ENST00000423902.7	NP_060250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD7	ENST00000423902.7	c.2376+43_2376+48dupTGGACT		intron_variant	Intron 5 of 37	5	NM_017780.4	ENSP00000392028.1

Frequencies

GnomAD3 genomes AF: 0.776 AC: 117300 AN: 151208 Hom.: 45725 Cov.: 0

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.806

Gnomad ASJ AF: 0.746

Gnomad EAS AF: 0.943

Gnomad SAS AF: 0.875

Gnomad FIN AF: 0.831

Gnomad MID AF: 0.732

Gnomad NFE AF: 0.772

Gnomad OTH AF: 0.754

GnomAD2 exomes AF: 0.801 AC: 166321 AN: 207726 AF XY: 0.802

Gnomad AFR exome AF: 0.732

Gnomad AMR exome AF: 0.820

Gnomad ASJ exome AF: 0.748

Gnomad EAS exome AF: 0.939

Gnomad FIN exome AF: 0.837

Gnomad NFE exome AF: 0.765

Gnomad OTH exome AF: 0.782

GnomAD4 exome AF: 0.776 AC: 1085308 AN: 1399472 Hom.: 423812 Cov.: 25 AF XY: 0.778 AC XY: 537772 AN XY: 691640

African (AFR) AF: 0.731 AC: 23041 AN: 31518

American (AMR) AF: 0.819 AC: 31192 AN: 38066

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 17640 AN: 23354

East Asian (EAS) AF: 0.949 AC: 36662 AN: 38632

South Asian (SAS) AF: 0.864 AC: 66138 AN: 76578

European-Finnish (FIN) AF: 0.835 AC: 43021 AN: 51516

Middle Eastern (MID) AF: 0.742 AC: 4077 AN: 5496

European-Non Finnish (NFE) AF: 0.760 AC: 818289 AN: 1076526

Other (OTH) AF: 0.783 AC: 45248 AN: 57786

GnomAD4 genome AF: 0.776 AC: 117374 AN: 151324 Hom.: 45749 Cov.: 0 AF XY: 0.784 AC XY: 57925 AN XY: 73918

African (AFR) AF: 0.729 AC: 30063 AN: 41236

American (AMR) AF: 0.805 AC: 12251 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.746 AC: 2581 AN: 3458

East Asian (EAS) AF: 0.943 AC: 4841 AN: 5136

South Asian (SAS) AF: 0.875 AC: 4210 AN: 4810

European-Finnish (FIN) AF: 0.831 AC: 8711 AN: 10488

Middle Eastern (MID) AF: 0.743 AC: 217 AN: 292

European-Non Finnish (NFE) AF: 0.772 AC: 52266 AN: 67702

Other (OTH) AF: 0.756 AC: 1587 AN: 2100

Alfa AF: 0.762 Hom.: 9294

Asia WGS AF: 0.900 AC: 3129 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

CHARGE syndrome Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Jun 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hypogonadotropic hypogonadism 5 with or without anosmia Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs5891777; hg19: chr8-61713126;