rs9434741

Variant names:

• chr1-6157799-A-G
• rs9434741
• NM_015557.3:c.387+1537T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015557.3(CHD5):​c.387+1537T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 152,066 control chromosomes in the GnomAD database, including 6,374 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (6374 hom., cov: 32)
• Consequence: CHD5 NM_015557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.86
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD5	NM_015557.3	c.387+1537T>C		intron_variant	Intron 3 of 41	ENST00000262450.8	NP_056372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD5	ENST00000262450.8	c.387+1537T>C		intron_variant	Intron 3 of 41	1	NM_015557.3	ENSP00000262450.3
CHD5	ENST00000496404.1	n.387+1537T>C		intron_variant	Intron 3 of 33	2		ENSP00000433676.1

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38598 AN: 151948 Hom.: 6348 Cov.: 32

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.223

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.254 AC: 38670 AN: 152066 Hom.: 6374 Cov.: 32 AF XY: 0.260 AC XY: 19298 AN XY: 74354

African (AFR) AF: 0.458 AC: 18983 AN: 41438

American (AMR) AF: 0.170 AC: 2599 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 662 AN: 3470

East Asian (EAS) AF: 0.284 AC: 1469 AN: 5164

South Asian (SAS) AF: 0.333 AC: 1608 AN: 4826

European-Finnish (FIN) AF: 0.277 AC: 2933 AN: 10570

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9756 AN: 67988

Other (OTH) AF: 0.223 AC: 470 AN: 2108

Alfa AF: 0.178 Hom.: 11821

Bravo AF: 0.254

Asia WGS AF: 0.307 AC: 1066 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.082
DANN	Benign	0.39
PhyloP100		-2.9
Mutation Taster		=100/0	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: rs9434741; hg19: chr1-6217859;