rs1483207

Variant names:

• chr8-60754721-C-G
• rs1483207
• NM_017780.4:c.1665+11624C>G

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+11624C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,236 control chromosomes in the GnomAD database, including 2,051 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 0.14 (2051 hom., cov: 32)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.751
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.262 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+11624C>G		intron	N/A	NP_060250.2
	CHD7	NM_001316690.1		c.1665+11624C>G		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+11624C>G		intron	N/A	ENSP00000392028.1
	CHD7	ENST00000524602.5	TSL:1	c.1665+11624C>G		intron	N/A	ENSP00000437061.1
	CHD7	ENST00000525508.1	TSL:5	c.1665+11624C>G		intron	N/A	ENSP00000436027.1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22018 AN: 152118 Hom.: 2049 Cov.: 32

Gnomad AFR AF: 0.0348

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.145 AC: 22025 AN: 152236 Hom.: 2051 Cov.: 32 AF XY: 0.145 AC XY: 10794 AN XY: 74444

African (AFR) AF: 0.0347 AC: 1443 AN: 41554

American (AMR) AF: 0.127 AC: 1942 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 501 AN: 3468

East Asian (EAS) AF: 0.274 AC: 1414 AN: 5170

South Asian (SAS) AF: 0.228 AC: 1099 AN: 4826

European-Finnish (FIN) AF: 0.165 AC: 1749 AN: 10598

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.197 AC: 13409 AN: 68006

Other (OTH) AF: 0.136 AC: 287 AN: 2112

Alfa AF: 0.165 Hom.: 307

Bravo AF: 0.136

Asia WGS AF: 0.249 AC: 862 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	12
DANN	Benign	0.60
PhyloP100		0.75
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1483207; hg19: chr8-61667280;