chr8-60788498-C-T

Variant names:

• chr8-60788498-C-T
• rs4237036
• NM_017780.4:c.2097-6488C>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.2097-6488C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 152,114 control chromosomes in the GnomAD database, including 25,592 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 0.53 (25592 hom., cov: 32)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 16 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.766 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.2097-6488C>T		intron	N/A	NP_060250.2
	CHD7	NM_001316690.1		c.1716+7448C>T		intron	N/A	NP_001303619.1	Q9P2D1-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD7	ENST00000423902.7	TSL:5 MANE Select	c.2097-6488C>T		intron	N/A	ENSP00000392028.1	Q9P2D1-1
	CHD7	ENST00000524602.5	TSL:1	c.1716+7448C>T		intron	N/A	ENSP00000437061.1	Q9P2D1-4
	CHD7	ENST00000933299.1		c.2097-6488C>T		intron	N/A	ENSP00000603358.1

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80274 AN: 151996 Hom.: 25585 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.785

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.687

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.539

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

GnomAD4 genome AF: 0.528 AC: 80289 AN: 152114 Hom.: 25592 Cov.: 32 AF XY: 0.537 AC XY: 39943 AN XY: 74392

African (AFR) AF: 0.147 AC: 6108 AN: 41494

American (AMR) AF: 0.628 AC: 9598 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 2155 AN: 3470

East Asian (EAS) AF: 0.786 AC: 4068 AN: 5176

South Asian (SAS) AF: 0.731 AC: 3530 AN: 4826

European-Finnish (FIN) AF: 0.687 AC: 7265 AN: 10576

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.673 AC: 45748 AN: 67980

Other (OTH) AF: 0.539 AC: 1133 AN: 2102

Alfa AF: 0.609 Hom.: 82662

Bravo AF: 0.505

Asia WGS AF: 0.682 AC: 2369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.093
DANN	Benign	0.16
PhyloP100		-1.4
Mutation Taster		=99/1	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: rs4237036; hg19: chr8-61701057;