Genetic Variant NM_015557.3:c.5589G>A (chr1-6106769-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_015557.3(CHD5):c.5589G>A(p.Gln1863Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000378 in 1,595,216 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: 𝑓 0.00027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00039 ( 0 hom. )

Consequence

CHD5
NM_015557.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.53

Publications

0 publications found

Variant links:

Genes affected

CHD5 (HGNC:16816): (chromodomain helicase DNA binding protein 5) This gene encodes a member of the chromodomain helicase DNA-binding protein family. Members of this family are characterized by a chromodomain, a helicase ATP-binding domain and an additional functional domain. This gene encodes a neuron-specific protein that may function in chromatin remodeling and gene transcription. This gene is a potential tumor suppressor gene that may play a role in the development of neuroblastoma. [provided by RefSeq, Feb 2012]

CHD5 Gene-Disease associations (from GenCC):

parenti-mignot neurodevelopmental syndrome
Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
schizophrenia
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

CHD5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 1-6106769-C-T is Benign according to our data. Variant chr1-6106769-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 729293.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.53 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000274 (41/149670) while in subpopulation AMR AF = 0.000333 (5/15020). AF 95% confidence interval is 0.000196. There are 0 homozygotes in GnomAd4. There are 19 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 41 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015557.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD5	NM_015557.3	MANE Select	c.5589G>A	p.Gln1863Gln	synonymous	Exon 39 of 42	NP_056372.1	Q8TDI0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHD5	ENST00000262450.8	TSL:1 MANE Select	c.5589G>A	p.Gln1863Gln	synonymous	Exon 39 of 42	ENSP00000262450.3	Q8TDI0
CHD5	ENST00000462991.5	TSL:1	n.*661G>A		non_coding_transcript_exon	Exon 29 of 31	ENSP00000466706.1	K7EMY3
CHD5	ENST00000496404.1	TSL:2	n.*629G>A		non_coding_transcript_exon	Exon 31 of 34	ENSP00000433676.1	F2Z2R5

Frequencies

GnomAD3 genomes

AF:

0.000274

AC:

AN:

149556

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000494

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000333

Gnomad ASJ

AF:

0.00347

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000214

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000296

Gnomad OTH

AF:

0.000487

GnomAD2 exomes

AF:

0.000569

AC:

140

AN:

245856

AF XY:

0.000673

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000552

Gnomad ASJ exome

AF:

0.00487

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000373

Gnomad OTH exome

AF:

0.00100

GnomAD4 exome

AF:

0.000389

AC:

562

AN:

1445546

Hom.:

Cov.:

AF XY:

0.000431

AC XY:

310

AN XY:

718874

show subpopulations

African (AFR)

AF:

0.0000605

AC:

AN:

33048

American (AMR)

AF:

0.000611

AC:

AN:

44220

Ashkenazi Jewish (ASJ)

AF:

0.00533

AC:

136

AN:

25500

East Asian (EAS)

AF:

0.00

AC:

AN:

38864

South Asian (SAS)

AF:

0.000966

AC:

AN:

85940

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50708

Middle Eastern (MID)

AF:

0.00317

AC:

AN:

5362

European-Non Finnish (NFE)

AF:

0.000210

AC:

231

AN:

1102580

Other (OTH)

AF:

0.00111

AC:

AN:

59324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

111

139

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000274

AC:

AN:

149670

Hom.:

Cov.:

AF XY:

0.000261

AC XY:

AN XY:

72904

show subpopulations

African (AFR)

AF:

0.0000493

AC:

AN:

40604

American (AMR)

AF:

0.000333

AC:

AN:

15020

Ashkenazi Jewish (ASJ)

AF:

0.00347

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5016

South Asian (SAS)

AF:

0.000215

AC:

AN:

4660

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10052

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000296

AC:

AN:

67596

Other (OTH)

AF:

0.000482

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000641

Hom.:

Bravo

AF:

0.000404

EpiCase

AF:

0.000436

EpiControl

AF:

0.000534

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

CHD5-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

8.0

(source)

DANN

Benign

0.87

PhyloP100

2.5

PromoterAI

-0.029

Neutral

(source)

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over