8-60702325-G-T

Variant names:

• chr8-60702325-G-T
• rs9643371
• NM_017780.4:c.-175+23243G>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017780.4(CHD7):​c.-175+23243G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 152,066 control chromosomes in the GnomAD database, including 35,260 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 0.66 (35260 hom., cov: 32)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.623

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.912 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD7	NM_017780.4	c.-175+23243G>T		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.-175+23243G>T		intron_variant	Intron 1 of 37	5	NM_017780.4	ENSP00000392028.1

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100327 AN: 151948 Hom.: 35253 Cov.: 32

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.934

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.661

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

GnomAD4 genome AF: 0.660 AC: 100364 AN: 152066 Hom.: 35260 Cov.: 32 AF XY: 0.670 AC XY: 49828 AN XY: 74332

Gnomad4 AFR AF: 0.406

Gnomad4 AMR AF: 0.739

Gnomad4 ASJ AF: 0.723

Gnomad4 EAS AF: 0.934

Gnomad4 SAS AF: 0.841

Gnomad4 FIN AF: 0.808

Gnomad4 NFE AF: 0.736

Gnomad4 OTH AF: 0.663

Alfa AF: 0.691 Hom.: 4714

Bravo AF: 0.639

Asia WGS AF: 0.844 AC: 2932 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.60
DANN	Benign	0.48

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: rs9643371; hg19: chr8-61614884;