rs2092507

Variant names:

• chr1-6104348-G-A
• rs2092507
• NM_015557.3:c.*1126C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-6104348-G-A
• chr1-6104348-G-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.*1126C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,288 control chromosomes in the GnomAD database, including 1,367 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 0.13 (1366 hom., cov: 32)
  • Exomes 𝑓: 0.13 (1 hom.)
• Consequence: CHD5 NM_015557.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.991
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.185 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD5	NM_015557.3	MANE Select	c.*1126C>T		3_prime_UTR	Exon 42 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.*1126C>T		3_prime_UTR	Exon 42 of 42	ENSP00000262450.3	Q8TDI0

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19784 AN: 152004 Hom.: 1366 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.0847

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.125

GnomAD4 exome AF: 0.127 AC: 21 AN: 166 Hom.: 1 Cov.: 0 AF XY: 0.0965 AC XY: 11 AN XY: 114

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 8

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AF: 0.333 AC: 2 AN: 6

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.108 AC: 14 AN: 130

Other (OTH) AF: 0.250 AC: 3 AN: 12

GnomAD4 genome AF: 0.130 AC: 19788 AN: 152122 Hom.: 1366 Cov.: 32 AF XY: 0.130 AC XY: 9692 AN XY: 74346

African (AFR) AF: 0.107 AC: 4437 AN: 41504

American (AMR) AF: 0.150 AC: 2293 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0847 AC: 294 AN: 3470

East Asian (EAS) AF: 0.193 AC: 994 AN: 5148

South Asian (SAS) AF: 0.196 AC: 944 AN: 4826

European-Finnish (FIN) AF: 0.161 AC: 1702 AN: 10596

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8734 AN: 67966

Other (OTH) AF: 0.126 AC: 266 AN: 2112

Alfa AF: 0.134 Hom.: 578

Bravo AF: 0.130

Asia WGS AF: 0.197 AC: 685 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.43
DANN	Benign	0.43
PhyloP100		-0.99
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: rs2092507; hg19: chr1-6164408;