rs12758341

Variant names:

• chr1-6101899-G-A
• rs12758341
• NM_015557.3:c.*3575C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-6101899-G-A
• chr1-6101899-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.*3575C>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 0.105 in 319,548 control chromosomes in the GnomAD database, including 2,293 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 0.096 (1013 hom., cov: 32)
  • Exomes 𝑓: 0.11 (1280 hom.)
• Consequence: CHD5 NM_015557.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.220
• 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: 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.342 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.*3575C>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.*3575C>T		3_prime_UTR	Exon 42 of 42	ENSP00000262450.3	Q8TDI0

Frequencies

GnomAD3 genomes AF: 0.0956 AC: 14553 AN: 152158 Hom.: 1019 Cov.: 32

Gnomad AFR AF: 0.0225

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.0803

Gnomad ASJ AF: 0.0997

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.0847

GnomAD2 exomes AF: 0.110 AC: 2972 AN: 27070 AF XY: 0.111

Gnomad AFR exome AF: 0.00855

Gnomad AMR exome AF: 0.0601

Gnomad ASJ exome AF: 0.0871

Gnomad EAS exome AF: 0.321

Gnomad FIN exome AF: 0.129

Gnomad NFE exome AF: 0.110

Gnomad OTH exome AF: 0.0881

GnomAD4 exome AF: 0.114 AC: 19124 AN: 167272 Hom.: 1280 Cov.: 0 AF XY: 0.116 AC XY: 11131 AN XY: 95590

African (AFR) AF: 0.0198 AC: 30 AN: 1514

American (AMR) AF: 0.0638 AC: 347 AN: 5442

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 434 AN: 4236

East Asian (EAS) AF: 0.355 AC: 474 AN: 1336

South Asian (SAS) AF: 0.133 AC: 5496 AN: 41446

European-Finnish (FIN) AF: 0.119 AC: 1164 AN: 9790

Middle Eastern (MID) AF: 0.0682 AC: 153 AN: 2244

European-Non Finnish (NFE) AF: 0.109 AC: 10196 AN: 93306

Other (OTH) AF: 0.104 AC: 830 AN: 7958

GnomAD4 genome AF: 0.0955 AC: 14544 AN: 152276 Hom.: 1013 Cov.: 32 AF XY: 0.0972 AC XY: 7239 AN XY: 74460

African (AFR) AF: 0.0224 AC: 931 AN: 41572

American (AMR) AF: 0.0801 AC: 1226 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0997 AC: 346 AN: 3470

East Asian (EAS) AF: 0.356 AC: 1839 AN: 5166

South Asian (SAS) AF: 0.149 AC: 718 AN: 4832

European-Finnish (FIN) AF: 0.124 AC: 1320 AN: 10614

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7837 AN: 68006

Other (OTH) AF: 0.0838 AC: 177 AN: 2112

Alfa AF: 0.0714 Hom.: 215

Bravo AF: 0.0889

Asia WGS AF: 0.208 AC: 723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.0
DANN	Benign	0.59
PhyloP100		-0.22
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: rs12758341; hg19: chr1-6161959; COSMIC: COSV51238665; COSMIC: COSV51238665;