chr1-6106769-C-T

Variant names:

• chr1-6106769-C-T
• rs147871474
• NM_015557.3:c.5589G>A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.53

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 -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 41 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD5	NM_015557.3	c.5589G>A	p.Gln1863Gln	synonymous_variant	Exon 39 of 42	ENST00000262450.8	NP_056372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD5	ENST00000262450.8	c.5589G>A	p.Gln1863Gln	synonymous_variant	Exon 39 of 42	1	NM_015557.3	ENSP00000262450.3
CHD5	ENST00000496404.1	n.*629G>A		non_coding_transcript_exon_variant	Exon 31 of 34	2		ENSP00000433676.1
CHD5	ENST00000496404.1	n.*629G>A		3_prime_UTR_variant	Exon 31 of 34	2		ENSP00000433676.1

Frequencies

GnomAD3 genomes AF: 0.000274 AC: 41 AN: 149556 Hom.: 0 Cov.: 32

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

GnomAD3 exomes AF: 0.000569 AC: 140 AN: 245856 Hom.: 0 AF XY: 0.000673 AC XY: 90 AN XY: 133794

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 SAS exome AF: 0.000854

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.: 0 Cov.: 34 AF XY: 0.000431 AC XY: 310 AN XY: 718874

Gnomad4 AFR exome AF: 0.0000605

Gnomad4 AMR exome AF: 0.000611

Gnomad4 ASJ exome AF: 0.00533

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000966

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000210

Gnomad4 OTH exome AF: 0.00111

GnomAD4 genome AF: 0.000274 AC: 41 AN: 149670 Hom.: 0 Cov.: 32 AF XY: 0.000261 AC XY: 19 AN XY: 72904

Gnomad4 AFR AF: 0.0000493

Gnomad4 AMR AF: 0.000333

Gnomad4 ASJ AF: 0.00347

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000215

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000296

Gnomad4 OTH AF: 0.000482

Alfa AF: 0.000641 Hom.: 0

Bravo AF: 0.000404

EpiCase AF: 0.000436

EpiControl AF: 0.000534

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 30, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

CHD5-related disorder Benign:1

Sep 26, 2024

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	8.0
DANN	Benign	0.87

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

LitVar

Other links and lift over

dbSNP: rs147871474; hg19: chr1-6166829;