rs4237036

Positions:

• chr8-60788498-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.2097-6488C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 152,114 control chromosomes in the GnomAD database, including 25,592 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 0.53 (25592 hom., cov: 32)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD7	NM_017780.4	c.2097-6488C>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.2097-6488C>T		intron_variant		5	NM_017780.4	ENSP00000392028	P1

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80274 AN: 151996 Hom.: 25585 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.785

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.687

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.539

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

GnomAD4 genome AF: 0.528 AC: 80289 AN: 152114 Hom.: 25592 Cov.: 32 AF XY: 0.537 AC XY: 39943 AN XY: 74392

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.628

Gnomad4 ASJ AF: 0.621

Gnomad4 EAS AF: 0.786

Gnomad4 SAS AF: 0.731

Gnomad4 FIN AF: 0.687

Gnomad4 NFE AF: 0.673

Gnomad4 OTH AF: 0.539

Alfa AF: 0.641 Hom.: 54990

Bravo AF: 0.505

Asia WGS AF: 0.682 AC: 2369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.093
DANN	Benign	0.16

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: rs4237036; hg19: chr8-61701057;