Variant 1-6105431-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_015557.3(CHD5):c.*47-4G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00341 in 470,492 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0033 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 6 hom. )

Consequence

CHD5
NM_015557.3 splice_region, intron

Scores

Splicing: ADA: 0.00006667

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0510

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 1-6105431-C-A is Benign according to our data. Variant chr1-6105431-C-A is described in ClinVar as [Benign]. Clinvar id is 2638116.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00334 (509/152330) while in subpopulation AMR AF= 0.00758 (116/15306). AF 95% confidence interval is 0.00646. There are 1 homozygotes in gnomad4. There are 239 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 509 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD5	NM_015557.3 linkuse as main transcript	c.*47-4G>T		splice_region_variant, intron_variant		ENST00000262450.8	NP_056372.1	Q8TDI0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHD5	ENST00000262450.8 linkuse as main transcript	c.*47-4G>T		splice_region_variant, intron_variant		1	NM_015557.3	ENSP00000262450.3		Q8TDI0
CHD5	ENST00000496404.1 linkuse as main transcript	n.*952-4G>T		splice_region_variant, intron_variant		2		ENSP00000433676.1		F2Z2R5

Frequencies

GnomAD3 genomes

AF:

0.00335

AC:

510

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000941

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00759

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00235

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.00407

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.00323

AC:

477

AN:

147536

Hom.:

AF XY:

0.00323

AC XY:

257

AN XY:

79530

show subpopulations

Gnomad AFR exome

AF:

0.000444

Gnomad AMR exome

AF:

0.00311

Gnomad ASJ exome

AF:

0.00550

Gnomad EAS exome

AF:

0.0000935

Gnomad SAS exome

AF:

0.00307

Gnomad FIN exome

AF:

0.00203

Gnomad NFE exome

AF:

0.00418

Gnomad OTH exome

AF:

0.00492

GnomAD4 exome

AF:

0.00344

AC:

1095

AN:

318162

Hom.:

Cov.:

AF XY:

0.00348

AC XY:

626

AN XY:

179764

show subpopulations

Gnomad4 AFR exome

AF:

0.000582

Gnomad4 AMR exome

AF:

0.00306

Gnomad4 ASJ exome

AF:

0.00501

Gnomad4 EAS exome

AF:

0.000109

Gnomad4 SAS exome

AF:

0.00293

Gnomad4 FIN exome

AF:

0.00231

Gnomad4 NFE exome

AF:

0.00380

Gnomad4 OTH exome

AF:

0.00497

GnomAD4 genome

AF:

0.00334

AC:

509

AN:

152330

Hom.:

Cov.:

AF XY:

0.00321

AC XY:

239

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000938

Gnomad4 AMR

AF:

0.00758

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00235

Gnomad4 NFE

AF:

0.00407

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00366

Hom.:

Bravo

AF:

0.00377

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

CHD5: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

4.2

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000067

dbscSNV1_RF

Benign

0.0080

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

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