1-6144101-G-A

Variant names:

• chr1-6144101-G-A
• rs17436816
• NM_015557.3:c.1857C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_015557.3(CHD5):​c.1857C>T​(p.Tyr619Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,614,092 control chromosomes in the GnomAD database, including 10,743 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.096 (918 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9825 hom.)
• Consequence: CHD5 NM_015557.3 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.39
• Publications: 17 publications found

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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• schizophrenia

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 1-6144101-G-A is Benign according to our data. Variant chr1-6144101-G-A is described in ClinVar as Benign. ClinVar VariationId is 3059081.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.38 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD5	NM_015557.3	MANE Select	c.1857C>T	p.Tyr619Tyr	synonymous	Exon 12 of 42	NP_056372.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD5	ENST00000262450.8	TSL:1 MANE Select	c.1857C>T	p.Tyr619Tyr	synonymous	Exon 12 of 42	ENSP00000262450.3
	CHD5	ENST00000462991.5	TSL:1	n.3C>T		non_coding_transcript_exon	Exon 1 of 31	ENSP00000466706.1
	CHD5	ENST00000496404.1	TSL:2	n.1857C>T		non_coding_transcript_exon	Exon 12 of 34	ENSP00000433676.1

Frequencies

GnomAD3 genomes AF: 0.0961 AC: 14618 AN: 152116 Hom.: 914 Cov.: 32

Gnomad AFR AF: 0.0315

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.0231

Gnomad SAS AF: 0.0961

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.127

GnomAD2 exomes AF: 0.117 AC: 29383 AN: 251484 AF XY: 0.118

Gnomad AFR exome AF: 0.0284

Gnomad AMR exome AF: 0.162

Gnomad ASJ exome AF: 0.218

Gnomad EAS exome AF: 0.0195

Gnomad FIN exome AF: 0.117

Gnomad NFE exome AF: 0.122

Gnomad OTH exome AF: 0.140

GnomAD4 exome AF: 0.111 AC: 162684 AN: 1461858 Hom.: 9825 Cov.: 46 AF XY: 0.112 AC XY: 81619 AN XY: 727226

African (AFR) AF: 0.0295 AC: 988 AN: 33480

American (AMR) AF: 0.165 AC: 7376 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 5586 AN: 26136

East Asian (EAS) AF: 0.0163 AC: 646 AN: 39700

South Asian (SAS) AF: 0.112 AC: 9657 AN: 86256

European-Finnish (FIN) AF: 0.114 AC: 6071 AN: 53416

Middle Eastern (MID) AF: 0.239 AC: 1379 AN: 5768

European-Non Finnish (NFE) AF: 0.112 AC: 124013 AN: 1111986

Other (OTH) AF: 0.115 AC: 6968 AN: 60392

GnomAD4 genome AF: 0.0962 AC: 14638 AN: 152234 Hom.: 918 Cov.: 32 AF XY: 0.0973 AC XY: 7240 AN XY: 74444

African (AFR) AF: 0.0315 AC: 1310 AN: 41552

American (AMR) AF: 0.165 AC: 2528 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 726 AN: 3470

East Asian (EAS) AF: 0.0228 AC: 118 AN: 5186

South Asian (SAS) AF: 0.0972 AC: 469 AN: 4824

European-Finnish (FIN) AF: 0.116 AC: 1230 AN: 10598

Middle Eastern (MID) AF: 0.212 AC: 62 AN: 292

European-Non Finnish (NFE) AF: 0.115 AC: 7849 AN: 68008

Other (OTH) AF: 0.129 AC: 271 AN: 2108

Alfa AF: 0.115 Hom.: 2832

Bravo AF: 0.0989

Asia WGS AF: 0.0810 AC: 281 AN: 3478

EpiCase AF: 0.129

EpiControl AF: 0.131

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

CHD5-related disorder Benign:1

Sep 26, 2023

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	1.3
DANN	Benign	0.60
PhyloP100		-1.4
Mutation Taster		=296/4	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17436816; hg19: chr1-6204161; COSMIC: COSV52419542;