rs41279496

Variant names:

• chr1-6149205-G-T
• rs41279496
• NM_015557.3:c.1161+41C>A

Variant summary

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

The NM_015557.3(CHD5):​c.1161+41C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0878 in 1,523,642 control chromosomes in the GnomAD database, including 8,402 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 0.092 (919 hom., cov: 30)
  • Exomes 𝑓: 0.087 (7483 hom.)
• Consequence: CHD5 NM_015557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.866
• Publications: 7 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD5	NM_015557.3	c.1161+41C>A		intron_variant	Intron 8 of 41	ENST00000262450.8	NP_056372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD5	ENST00000262450.8	c.1161+41C>A		intron_variant	Intron 8 of 41	1	NM_015557.3	ENSP00000262450.3
CHD5	ENST00000496404.1	n.1161+41C>A		intron_variant	Intron 8 of 33	2		ENSP00000433676.1

Frequencies

GnomAD3 genomes AF: 0.0921 AC: 13965 AN: 151634 Hom.: 914 Cov.: 30

Gnomad AFR AF: 0.0643

Gnomad AMI AF: 0.0593

Gnomad AMR AF: 0.0836

Gnomad ASJ AF: 0.0896

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0715

Gnomad OTH AF: 0.0818

GnomAD2 exomes AF: 0.125 AC: 21411 AN: 171002 AF XY: 0.126

Gnomad AFR exome AF: 0.0654

Gnomad AMR exome AF: 0.119

Gnomad ASJ exome AF: 0.0862

Gnomad EAS exome AF: 0.247

Gnomad FIN exome AF: 0.239

Gnomad NFE exome AF: 0.0804

Gnomad OTH exome AF: 0.114

GnomAD4 exome AF: 0.0873 AC: 119832 AN: 1371890 Hom.: 7483 Cov.: 36 AF XY: 0.0900 AC XY: 60431 AN XY: 671756

African (AFR) AF: 0.0622 AC: 1930 AN: 31038

American (AMR) AF: 0.109 AC: 3779 AN: 34762

Ashkenazi Jewish (ASJ) AF: 0.0884 AC: 1954 AN: 22116

East Asian (EAS) AF: 0.310 AC: 11506 AN: 37158

South Asian (SAS) AF: 0.168 AC: 12482 AN: 74444

European-Finnish (FIN) AF: 0.229 AC: 11172 AN: 48748

Middle Eastern (MID) AF: 0.124 AC: 547 AN: 4424

European-Non Finnish (NFE) AF: 0.0672 AC: 71377 AN: 1062806

Other (OTH) AF: 0.0902 AC: 5085 AN: 56394

GnomAD4 genome AF: 0.0921 AC: 13977 AN: 151752 Hom.: 919 Cov.: 30 AF XY: 0.101 AC XY: 7485 AN XY: 74128

African (AFR) AF: 0.0643 AC: 2660 AN: 41398

American (AMR) AF: 0.0836 AC: 1275 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.0896 AC: 311 AN: 3470

East Asian (EAS) AF: 0.256 AC: 1309 AN: 5116

South Asian (SAS) AF: 0.179 AC: 858 AN: 4798

European-Finnish (FIN) AF: 0.234 AC: 2458 AN: 10520

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0715 AC: 4852 AN: 67884

Other (OTH) AF: 0.0829 AC: 175 AN: 2112

Alfa AF: 0.0828 Hom.: 110

Bravo AF: 0.0798

Asia WGS AF: 0.205 AC: 712 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.7
DANN	Benign	0.64
PhyloP100		0.87
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: rs41279496; hg19: chr1-6209265; COSMIC: COSV52424375;