chr8-60678764-C-CGCG

Variant names:

• chr8-60678764-C-CGCG
• rs886063023
• NM_017780.4:c.-469_-467dupGGC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_017780.4(CHD7):​c.-469_-467dupGGC 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
• Publications: 2 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: Orphanet, G2P, Labcorp Genetics (formerly Invitae), Broad Center for Mendelian Genomics, ClinGen
• 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017780.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD7	NM_017780.4	MANE Select	c.-469_-467dupGGC		5_prime_UTR	Exon 1 of 38	NP_060250.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD7	ENST00000423902.7	TSL:5 MANE Select	c.-469_-467dupGGC		5_prime_UTR	Exon 1 of 38	ENSP00000392028.1	Q9P2D1-1
	CHD7	ENST00000933299.1		c.-469_-467dupGGC		5_prime_UTR	Exon 1 of 38	ENSP00000603358.1
	CHD7	ENST00000933298.1		c.-469_-467dupGGC		5_prime_UTR	Exon 1 of 38	ENSP00000603357.1

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

African (AFR) AF: 0.500 AC: 2 AN: 4

American (AMR) AF: 0.750 AC: 3 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.563 AC: 225 AN: 400

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.351 AC: 66 AN: 188

Other (OTH) AF: 0.500 AC: 3 AN: 6

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

African (AFR) AF: 0.655 AC: 24674 AN: 37680

American (AMR) AF: 0.669 AC: 9521 AN: 14230

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 2128 AN: 3302

East Asian (EAS) AF: 0.693 AC: 3072 AN: 4432

South Asian (SAS) AF: 0.692 AC: 3063 AN: 4428

European-Finnish (FIN) AF: 0.733 AC: 5392 AN: 7358

Middle Eastern (MID) AF: 0.527 AC: 137 AN: 260

European-Non Finnish (NFE) AF: 0.629 AC: 39634 AN: 62994

Other (OTH) AF: 0.649 AC: 1227 AN: 1892

Alfa AF: 0.539 Hom.: 1058

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	CHARGE syndrome (1)
-	1	-	Hypogonadism with anosmia (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.40

Splicing

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

Other links and lift over

dbSNP: rs886063023; hg19: chr8-61591323;