rs45461501

Positions:

• chr8-60828630-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_017780.4(CHD7):​c.3379-33A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00682 in 1,575,736 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0047 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0070 (32 hom.)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.08

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 8-60828630-A-G is Benign according to our data. Variant chr8-60828630-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 260902.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0047 (716/152264) while in subpopulation AMR AF= 0.00909 (139/15294). AF 95% confidence interval is 0.00786. There are 5 homozygotes in gnomad4. There are 348 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 716 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD7	NM_017780.4	c.3379-33A>G		intron_variant		ENST00000423902.7	NP_060250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHD7	ENST00000423902.7	c.3379-33A>G		intron_variant		5	NM_017780.4	ENSP00000392028.1
CHD7	ENST00000524602.5	c.1717-33599A>G		intron_variant		1		ENSP00000437061.1
CHD7	ENST00000695853.1	n.3379-33A>G		intron_variant				ENSP00000512218.1

Frequencies

GnomAD3 genomes AF: 0.00471 AC: 716 AN: 152146 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00910

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00123

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00722

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00440 AC: 923 AN: 209898 Hom.: 2 AF XY: 0.00463 AC XY: 524 AN XY: 113236

Gnomad AFR exome AF: 0.00125

Gnomad AMR exome AF: 0.00400

Gnomad ASJ exome AF: 0.000121

Gnomad EAS exome AF: 0.0000651

Gnomad SAS exome AF: 0.00216

Gnomad FIN exome AF: 0.00119

Gnomad NFE exome AF: 0.00725

Gnomad OTH exome AF: 0.00426

GnomAD4 exome AF: 0.00705 AC: 10030 AN: 1423472 Hom.: 32 Cov.: 30 AF XY: 0.00688 AC XY: 4847 AN XY: 704496

Gnomad4 AFR exome AF: 0.000942

Gnomad4 AMR exome AF: 0.00353

Gnomad4 ASJ exome AF: 0.000527

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00212

Gnomad4 FIN exome AF: 0.00138

Gnomad4 NFE exome AF: 0.00840

Gnomad4 OTH exome AF: 0.00720

GnomAD4 genome AF: 0.00470 AC: 716 AN: 152264 Hom.: 5 Cov.: 32 AF XY: 0.00467 AC XY: 348 AN XY: 74456

Gnomad4 AFR AF: 0.00116

Gnomad4 AMR AF: 0.00909

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00269

Gnomad4 FIN AF: 0.00123

Gnomad4 NFE AF: 0.00722

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00568 Hom.: 0

Bravo AF: 0.00481

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.17
DANN	Benign	0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs45461501; hg19: chr8-61741189;