rs10092214

Positions:

• chr8-60814320-G-A

Variant summary

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

The NM_017780.4(CHD7):​c.2499-2067G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 152,140 control chromosomes in the GnomAD database, including 13,340 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 0.38 (13340 hom., cov: 33)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.653

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHD7	NM_017780.4	c.2499-2067G>A		intron_variant		ENST00000423902.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHD7	ENST00000423902.7	c.2499-2067G>A		intron_variant		5	NM_017780.4	P1
CHD7	ENST00000524602.5	c.1716+33270G>A		intron_variant		1
CHD7	ENST00000525508.1	c.2499-2067G>A		intron_variant		5
CHD7	ENST00000695853.1	c.2499-2067G>A		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57406 AN: 152022 Hom.: 13339 Cov.: 33

Gnomad AFR AF: 0.0955

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.377 AC: 57419 AN: 152140 Hom.: 13340 Cov.: 33 AF XY: 0.386 AC XY: 28711 AN XY: 74344

Gnomad4 AFR AF: 0.0953

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.490

Gnomad4 EAS AF: 0.503

Gnomad4 SAS AF: 0.504

Gnomad4 FIN AF: 0.522

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.403

Alfa AF: 0.460 Hom.: 32697

Bravo AF: 0.363

Asia WGS AF: 0.429 AC: 1492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.32
DANN	Benign	0.34

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: rs10092214; hg19: chr8-61726879;