1-6152881-G-A

Variant names:

• chr1-6152881-G-A
• rs1883603
• NM_015557.3:c.746-345C>T

Variant summary

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

The NM_015557.3(CHD5):​c.746-345C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0856 in 152,310 control chromosomes in the GnomAD database, including 657 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 0.086 (657 hom., cov: 33)
• Consequence: CHD5 NM_015557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.903
• Publications: 2 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD5	NM_015557.3	c.746-345C>T		intron_variant	Intron 5 of 41	ENST00000262450.8	NP_056372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD5	ENST00000262450.8	c.746-345C>T		intron_variant	Intron 5 of 41	1	NM_015557.3	ENSP00000262450.3
CHD5	ENST00000496404.1	n.746-345C>T		intron_variant	Intron 5 of 33	2		ENSP00000433676.1

Frequencies

GnomAD3 genomes AF: 0.0857 AC: 13036 AN: 152192 Hom.: 653 Cov.: 33

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.0535

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0114

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.0540

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0706

Gnomad OTH AF: 0.0879

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

GnomAD4 genome AF: 0.0856 AC: 13045 AN: 152310 Hom.: 657 Cov.: 33 AF XY: 0.0843 AC XY: 6276 AN XY: 74482

African (AFR) AF: 0.134 AC: 5553 AN: 41544

American (AMR) AF: 0.0534 AC: 817 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 352 AN: 3470

East Asian (EAS) AF: 0.0114 AC: 59 AN: 5184

South Asian (SAS) AF: 0.125 AC: 604 AN: 4828

European-Finnish (FIN) AF: 0.0540 AC: 573 AN: 10620

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0706 AC: 4801 AN: 68038

Other (OTH) AF: 0.0874 AC: 185 AN: 2116

Alfa AF: 0.0799 Hom.: 183

Bravo AF: 0.0854

Asia WGS AF: 0.0620 AC: 215 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.023
DANN	Benign	0.50
PhyloP100		-0.90
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: rs1883603; hg19: chr1-6212941;