rs7843033

Variant names:

• chr8-60759956-A-C
• rs7843033
• NM_017780.4:c.1665+16859A>C

Your query was ambiguous. Multiple possible variants found:

• chr8-60759956-A-C
• chr8-60759956-A-G
• chr8-60759956-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017780.4(CHD7):​c.1665+16859A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 151,994 control chromosomes in the GnomAD database, including 45,491 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.77 (45491 hom., cov: 30)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.652
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.919 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD7	NM_017780.4	MANE Select	c.1665+16859A>C		intron	N/A	NP_060250.2
	CHD7	NM_001316690.1		c.1665+16859A>C		intron	N/A	NP_001303619.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD7	ENST00000423902.7	TSL:5 MANE Select	c.1665+16859A>C		intron	N/A	ENSP00000392028.1
	CHD7	ENST00000524602.5	TSL:1	c.1665+16859A>C		intron	N/A	ENSP00000437061.1
	CHD7	ENST00000525508.1	TSL:5	c.1665+16859A>C		intron	N/A	ENSP00000436027.1

Frequencies

GnomAD3 genomes AF: 0.771 AC: 117152 AN: 151876 Hom.: 45471 Cov.: 30

Gnomad AFR AF: 0.724

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.760

Gnomad EAS AF: 0.941

Gnomad SAS AF: 0.914

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.765

Gnomad OTH AF: 0.760

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.771 AC: 117219 AN: 151994 Hom.: 45491 Cov.: 30 AF XY: 0.779 AC XY: 57906 AN XY: 74292

African (AFR) AF: 0.723 AC: 29944 AN: 41418

American (AMR) AF: 0.794 AC: 12112 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.760 AC: 2635 AN: 3468

East Asian (EAS) AF: 0.941 AC: 4858 AN: 5160

South Asian (SAS) AF: 0.914 AC: 4400 AN: 4812

European-Finnish (FIN) AF: 0.829 AC: 8774 AN: 10580

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.765 AC: 52019 AN: 67974

Other (OTH) AF: 0.762 AC: 1610 AN: 2112

Alfa AF: 0.762 Hom.: 6706

Bravo AF: 0.761

Asia WGS AF: 0.909 AC: 3160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.81
DANN	Benign	0.24
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7843033; hg19: chr8-61672515;