Variant rs1206578296 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4BP6

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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CHD7
NM_017780.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 1.13

Variant links:

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]

CHD7 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1

In a domain Helicase ATP-binding (size 174) in uniprot entity CHD7_HUMAN there are 15 pathogenic changes around while only 1 benign (94%) in NM_017780.4

PM2

Very rare variant in population databases, with high coverage;

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 [Conflicting_classifications_of_pathogenicity]. Clinvar id is 529125.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD7	NM_017780.4 link	c.3030A>G	p.Ile1010Met	missense_variant	12/38	ENST00000423902.7	NP_060250.2	Q9P2D1-1Q6ZWF9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CHD7	ENST00000423902.7 link	c.3030A>G	p.Ile1010Met	missense_variant	12/38	5	NM_017780.4	ENSP00000392028.1	Q9P2D1-1
CHD7	ENST00000524602.5 link	c.1717-39654A>G		intron_variant		1		ENSP00000437061.1	Q9P2D1-4
CHD7	ENST00000525508.1 link	c.3030A>G	p.Ile1010Met	missense_variant	11/12	5		ENSP00000436027.1	Q9P2D1-2
CHD7	ENST00000695853.1 link	n.3030A>G		non_coding_transcript_exon_variant	12/37			ENSP00000512218.1	A0A8Q3WKT9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249160

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135170

show subpopulations

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:

AN:

1461412

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727010

show subpopulations

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.:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

CHARGE syndrome;C3552553:Hypogonadotropic hypogonadism 5 with or without anosmia

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Mar 26, 2024

- -

CHARGE syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 03, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Uncertain

0.097

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.63

D;.

Eigen

Benign

-0.075

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.061

MetaRNN

Benign

0.35

T;T

MetaSVM

Uncertain

0.39

MutationAssessor

Benign

1.2

L;L

PrimateAI

Pathogenic

0.84

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over