rs1206578296

chr8-60822575-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 3P and 3B. PM2 PP2 BP4 BP6_Moderate

The NM_017780.4(CHD7):c.3030A>G(p.Ile1010Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CHD7 NM_017780.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.13

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, CHD7
• BP4: Computational evidence support a benign effect (MetaRNN=0.35338268).
• BP6: Variant 8-60822575-A-G is Benign according to our data. Variant chr8-60822575-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 529125.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHD7	NM_017780.4	c.3030A>G	p.Ile1010Met	missense_variant	12/38	ENST00000423902.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHD7	ENST00000423902.7	c.3030A>G	p.Ile1010Met	missense_variant	12/38	5	NM_017780.4	P1
CHD7	ENST00000524602.5	c.1717-39654A>G		intron_variant		1
CHD7	ENST00000525508.1	c.3030A>G	p.Ile1010Met	missense_variant	11/12	5
CHD7	ENST00000695853.1	c.3030A>G	p.Ile1010Met	missense_variant, NMD_transcript_variant	12/37

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249160 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135170

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461412 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727010

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

CHARGE syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 03, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.097	D
BayesDel_noAF	Uncertain	-0.020
Cadd	Benign	22
Dann	Uncertain	0.99
DEOGEN2	Uncertain	0.63	D;.
Eigen	Benign	-0.075
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.35	T;T
MetaSVM	Uncertain	0.39	D
MutationAssessor	Benign	1.2	L;L
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-2.1	N;N
REVEL	Uncertain	0.42
Sift	Benign	0.035	D;D
Sift4G	Benign	0.16	T;T
Polyphen		0.051	B;B
Vest4		0.77
MutPred		0.57		Loss of catalytic residue at I1010 (P = 0.0054);Loss of catalytic residue at I1010 (P = 0.0054);
MVP		0.86
MPC		0.98
ClinPred		0.22	T
GERP RS		5.5
Varity_R		0.47
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1206578296; hg19: chr8-61735134;