rs4392940

Variant names:

• chr8-60787372-G-A
• rs4392940
• NM_017780.4:c.2096+5942G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-60787372-G-A
• chr8-60787372-G-C

Variant summary

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

The NM_017780.4(CHD7):​c.2096+5942G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.838 in 152,162 control chromosomes in the GnomAD database, including 53,875 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 0.84 (53875 hom., cov: 30)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.87
• Publications: 3 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 = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD7	NM_017780.4	c.2096+5942G>A		intron_variant	Intron 3 of 37	ENST00000423902.7	NP_060250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD7	ENST00000423902.7	c.2096+5942G>A		intron_variant	Intron 3 of 37	5	NM_017780.4	ENSP00000392028.1

Frequencies

GnomAD3 genomes AF: 0.838 AC: 127439 AN: 152044 Hom.: 53829 Cov.: 30

Gnomad AFR AF: 0.933

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.764

Gnomad EAS AF: 0.943

Gnomad SAS AF: 0.918

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.776

Gnomad OTH AF: 0.812

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

GnomAD4 genome AF: 0.838 AC: 127542 AN: 152162 Hom.: 53875 Cov.: 30 AF XY: 0.845 AC XY: 62829 AN XY: 74374

African (AFR) AF: 0.932 AC: 38720 AN: 41530

American (AMR) AF: 0.829 AC: 12669 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.764 AC: 2651 AN: 3470

East Asian (EAS) AF: 0.943 AC: 4881 AN: 5176

South Asian (SAS) AF: 0.918 AC: 4427 AN: 4824

European-Finnish (FIN) AF: 0.832 AC: 8807 AN: 10580

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.776 AC: 52777 AN: 67996

Other (OTH) AF: 0.814 AC: 1717 AN: 2110

Alfa AF: 0.824 Hom.: 7403

Bravo AF: 0.836

Asia WGS AF: 0.930 AC: 3231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0040
DANN	Benign	0.66
PhyloP100		-2.9
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: rs4392940; hg19: chr8-61699931;