rs13256023

Positions:

• chr8-60735992-C-T

Variant summary

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

The NM_017780.4(CHD7):​c.-174-5267C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,076 control chromosomes in the GnomAD database, including 7,576 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 0.28 (7576 hom., cov: 32)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD7	NM_017780.4	c.-174-5267C>T		intron_variant		ENST00000423902.7	NP_060250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHD7	ENST00000423902.7	c.-174-5267C>T		intron_variant		5	NM_017780.4	ENSP00000392028	P1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42152 AN: 151958 Hom.: 7567 Cov.: 32

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.277 AC: 42191 AN: 152076 Hom.: 7576 Cov.: 32 AF XY: 0.273 AC XY: 20290 AN XY: 74326

Gnomad4 AFR AF: 0.511

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.252

Alfa AF: 0.199 Hom.: 6716

Bravo AF: 0.290

Asia WGS AF: 0.192 AC: 672 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.43
DANN	Benign	0.67

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: rs13256023; hg19: chr8-61648551;