rs6471895

Positions:

• chr8-60712390-T-C

Variant summary

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

The NM_017780.4(CHD7):​c.-174-28869T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0965 in 152,238 control chromosomes in the GnomAD database, including 1,515 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 0.096 (1515 hom., cov: 32)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.441

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHD7	NM_017780.4	c.-174-28869T>C		intron_variant		ENST00000423902.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHD7	ENST00000423902.7	c.-174-28869T>C		intron_variant		5	NM_017780.4	P1

Frequencies

GnomAD3 genomes AF: 0.0964 AC: 14669 AN: 152120 Hom.: 1512 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0512

Gnomad ASJ AF: 0.0392

Gnomad EAS AF: 0.00769

Gnomad SAS AF: 0.0681

Gnomad FIN AF: 0.0243

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0329

Gnomad OTH AF: 0.0824

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

GnomAD4 genome AF: 0.0965 AC: 14690 AN: 152238 Hom.: 1515 Cov.: 32 AF XY: 0.0943 AC XY: 7019 AN XY: 74446

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.0510

Gnomad4 ASJ AF: 0.0392

Gnomad4 EAS AF: 0.00752

Gnomad4 SAS AF: 0.0671

Gnomad4 FIN AF: 0.0243

Gnomad4 NFE AF: 0.0329

Gnomad4 OTH AF: 0.0829

Alfa AF: 0.0685 Hom.: 139

Bravo AF: 0.104

Asia WGS AF: 0.0540 AC: 190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6471895; hg19: chr8-61624949;