1-6105431-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_015557.3(CHD5):c.*47-4G>T variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00006667
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0510

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]

ACMG classification

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 GnomAd at 510 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHD5	NM_015557.3	c.*47-4G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000262450.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHD5	ENST00000262450.8	c.*47-4G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_015557.3	P1

Frequencies

GnomAD3 genomes AF: 0.00335 AC: 510 AN: 152212 Hom.: 1 Cov.: 32

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.: 2 AF XY: 0.00323 AC XY: 257 AN XY: 79530

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.: 6 Cov.: 0 AF XY: 0.00348 AC XY: 626 AN XY: 179764

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.: 1 Cov.: 32 AF XY: 0.00321 AC XY: 239 AN XY: 74484

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.: 0

Bravo AF: 0.00377

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

Other links and lift over

dbSNP: rs12138820; hg19: chr1-6165491;