14-21385470-ATTTTTT-ATTTTTTT

Variant names:

• chr14-21385470-A-AT
• rs370612022
• NM_001170629.2:c.*142dupA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001170629.2(CHD8):​c.*142dupA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0808 in 1,043,612 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0023 (0 hom., cov: 31)
  • Exomes 𝑓: 0.093 (0 hom.)
• Consequence: CHD8 NM_001170629.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06

Genes affected

CHD8 (HGNC:20153): (chromodomain helicase DNA binding protein 8) This gene encodes a member of the chromodomain-helicase-DNA binding protein family, which is characterized by a SNF2-like domain and two chromatin organization modifier domains. The encoded protein also contains brahma and kismet domains, which are common to the subfamily of chromodomain-helicase-DNA binding proteins to which this protein belongs. This gene has been shown to function in several processes that include transcriptional regulation, epigenetic remodeling, promotion of cell proliferation, and regulation of RNA synthesis. Allelic variants of this gene are associated with autism spectrum disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2016]

LOC107984643 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD8	NM_001170629.2	c.*142dupA		3_prime_UTR_variant	Exon 38 of 38	ENST00000646647.2	NP_001164100.1
CHD8	NM_020920.4	c.*142dupA		3_prime_UTR_variant	Exon 38 of 38		NP_065971.2
LOC107984643	XR_001750627.2	n.441+772dupT		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD8	ENST00000646647	c.*142dupA		3_prime_UTR_variant	Exon 38 of 38		NM_001170629.2	ENSP00000495240.1

Frequencies

GnomAD3 genomes AF: 0.00229 AC: 317 AN: 138696 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00158

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000721

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.00676

Gnomad SAS AF: 0.00320

Gnomad FIN AF: 0.00476

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00212

Gnomad OTH AF: 0.00582

GnomAD4 exome AF: 0.0929 AC: 84041 AN: 904888 Hom.: 0 Cov.: 0 AF XY: 0.0919 AC XY: 40711 AN XY: 443028

Gnomad4 AFR exome AF: 0.0631

Gnomad4 AMR exome AF: 0.0773

Gnomad4 ASJ exome AF: 0.0750

Gnomad4 EAS exome AF: 0.0768

Gnomad4 SAS exome AF: 0.0924

Gnomad4 FIN exome AF: 0.0703

Gnomad4 NFE exome AF: 0.0962

Gnomad4 OTH exome AF: 0.0885

GnomAD4 genome AF: 0.00231 AC: 320 AN: 138724 Hom.: 0 Cov.: 31 AF XY: 0.00239 AC XY: 160 AN XY: 67046

Gnomad4 AFR AF: 0.00168

Gnomad4 AMR AF: 0.000793

Gnomad4 ASJ AF: 0.00519

Gnomad4 EAS AF: 0.00678

Gnomad4 SAS AF: 0.00275

Gnomad4 FIN AF: 0.00476

Gnomad4 NFE AF: 0.00212

Gnomad4 OTH AF: 0.00579

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs370612022; hg19: chr14-21853629;