chr1-6106445-G-A

Variant names:

• chr1-6106445-G-A
• rs764604388
• NM_015557.3:c.5807C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_015557.3(CHD5):​c.5807C>T​(p.Pro1936Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000763 in 1,572,390 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000070 (0 hom.)
• Consequence: CHD5 NM_015557.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.04
• Publications: 0 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• schizophrenia

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

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.4187126).
• BS2: High AC in GnomAdExome4 at 10 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.5807C>T	p.Pro1936Leu	missense	Exon 40 of 42	NP_056372.1	Q8TDI0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD5	ENST00000262450.8	TSL:1 MANE Select	c.5807C>T	p.Pro1936Leu	missense	Exon 40 of 42	ENSP00000262450.3	Q8TDI0
	CHD5	ENST00000496404.1	TSL:2	n.*847C>T		non_coding_transcript_exon	Exon 32 of 34	ENSP00000433676.1	F2Z2R5
	CHD5	ENST00000496404.1	TSL:2	n.*847C>T		3_prime_UTR	Exon 32 of 34	ENSP00000433676.1	F2Z2R5

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152226 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000546 AC: 1 AN: 183070 AF XY: 0.0000102

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000373

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000704 AC: 10 AN: 1420164 Hom.: 0 Cov.: 34 AF XY: 0.00000569 AC XY: 4 AN XY: 703250

African (AFR) AF: 0.00 AC: 0 AN: 32372

American (AMR) AF: 0.0000263 AC: 1 AN: 38016

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25486

East Asian (EAS) AF: 0.00 AC: 0 AN: 36996

South Asian (SAS) AF: 0.00 AC: 0 AN: 82090

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 0.00000825 AC: 9 AN: 1091350

Other (OTH) AF: 0.00 AC: 0 AN: 58814

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152226 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74364

African (AFR) AF: 0.0000241 AC: 1 AN: 41468

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000170 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Benign	0.044
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.42	T
MetaSVM	Uncertain	-0.068	T
MutationAssessor	Benign	0.81	L
PhyloP100		4.0
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.37
Sift	Benign	0.094	T
Sift4G	Benign	0.23	T
Polyphen		0.19	B
Vest4		0.65
MutPred		0.36		Loss of disorder (P = 0.0067)
MVP		0.59
MPC		1.6
ClinPred		0.72	D
GERP RS		4.9
PromoterAI		0.021	Neutral
Varity_R		0.22
gMVP		0.61
Mutation Taster		=82/18	polymorphism

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: rs764604388; hg19: chr1-6166505; COSMIC: COSV52410740;