rs4288413

Variant names:

• chr8-60739585-G-A
• rs4288413
• NM_017780.4:c.-174-1674G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-60739585-G-A
• chr8-60739585-G-C
• chr8-60739585-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_017780.4(CHD7):​c.-174-1674G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 152,044 control chromosomes in the GnomAD database, including 19,690 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 0.46 (19690 hom., cov: 33)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.535
• 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: 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.763 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.-174-1674G>A		intron	N/A	NP_060250.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD7	ENST00000423902.7	TSL:5 MANE Select	c.-174-1674G>A		intron	N/A	ENSP00000392028.1	Q9P2D1-1
	CHD7	ENST00000933299.1		c.-174-1674G>A		intron	N/A	ENSP00000603358.1
	CHD7	ENST00000933300.1		c.-174-1674G>A		intron	N/A	ENSP00000603359.1

Frequencies

GnomAD3 genomes AF: 0.461 AC: 70084 AN: 151924 Hom.: 19685 Cov.: 33

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.782

Gnomad SAS AF: 0.713

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.461 AC: 70104 AN: 152044 Hom.: 19690 Cov.: 33 AF XY: 0.474 AC XY: 35191 AN XY: 74308

African (AFR) AF: 0.129 AC: 5332 AN: 41474

American (AMR) AF: 0.550 AC: 8408 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.527 AC: 1826 AN: 3466

East Asian (EAS) AF: 0.783 AC: 4059 AN: 5182

South Asian (SAS) AF: 0.713 AC: 3443 AN: 4826

European-Finnish (FIN) AF: 0.640 AC: 6753 AN: 10550

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.570 AC: 38742 AN: 67956

Other (OTH) AF: 0.477 AC: 1005 AN: 2106

Alfa AF: 0.532 Hom.: 37746

Bravo AF: 0.437

Asia WGS AF: 0.673 AC: 2336 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	13
DANN	Benign	0.60
PhyloP100		0.54
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: rs4288413; hg19: chr8-61652144;