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. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD7	NM_017780.4	c.-174-1674G>A		intron_variant	Intron 1 of 37	ENST00000423902.7	NP_060250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD7	ENST00000423902.7	c.-174-1674G>A		intron_variant	Intron 1 of 37	5	NM_017780.4	ENSP00000392028.1

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

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.550

Gnomad4 ASJ AF: 0.527

Gnomad4 EAS AF: 0.783

Gnomad4 SAS AF: 0.713

Gnomad4 FIN AF: 0.640

Gnomad4 NFE AF: 0.570

Gnomad4 OTH AF: 0.477

Alfa AF: 0.545 Hom.: 30796

Bravo AF: 0.437

Asia WGS AF: 0.673 AC: 2336 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	13
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs4288413; hg19: chr8-61652144;