rs12754299

Positions:

• chr1-6129393-G-A
• chr1-6129393-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015557.3(CHD5):​c.3388-324C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,178 control chromosomes in the GnomAD database, including 1,172 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 0.11 (1172 hom., cov: 32)
• Consequence: CHD5 NM_015557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.984

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD5	NM_015557.3	c.3388-324C>T		intron_variant		ENST00000262450.8	NP_056372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHD5	ENST00000262450.8	c.3388-324C>T		intron_variant		1	NM_015557.3	ENSP00000262450	P1
CHD5	ENST00000462991.5	c.1535-324C>T		intron_variant, NMD_transcript_variant		1		ENSP00000466706
CHD5	ENST00000377999.5	c.291-324C>T		intron_variant, NMD_transcript_variant		2		ENSP00000367238
CHD5	ENST00000496404.1	c.3388-324C>T		intron_variant, NMD_transcript_variant		2		ENSP00000433676

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17076 AN: 152060 Hom.: 1175 Cov.: 32

Gnomad AFR AF: 0.0526

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.0879

Gnomad ASJ AF: 0.0984

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.0999

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

GnomAD4 genome AF: 0.112 AC: 17079 AN: 152178 Hom.: 1172 Cov.: 32 AF XY: 0.113 AC XY: 8435 AN XY: 74386

Gnomad4 AFR AF: 0.0527

Gnomad4 AMR AF: 0.0877

Gnomad4 ASJ AF: 0.0984

Gnomad4 EAS AF: 0.330

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.0989

Alfa AF: 0.0647 Hom.: 92

Bravo AF: 0.106

Asia WGS AF: 0.193 AC: 672 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	0.021
DANN	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs12754299; hg19: chr1-6189453;