14-21385470-ATTTTTT-ATTTT

Variant names:

• chr14-21385470-ATT-A
• rs370612022
• NM_001170629.2:c.*141_*142delAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001170629.2(CHD8):​c.*141_*142delAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00652 in 1,042,244 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 0.00011 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0075 (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.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000108 (15/138810) while in subpopulation AFR AF= 0.000367 (14/38114). AF 95% confidence interval is 0.000221. There are 0 homozygotes in gnomad4. There are 6 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD8	NM_001170629.2	c.*141_*142delAA		3_prime_UTR_variant	Exon 38 of 38	ENST00000646647.2	NP_001164100.1
CHD8	NM_020920.4	c.*141_*142delAA		3_prime_UTR_variant	Exon 38 of 38		NP_065971.2
LOC107984643	XR_001750627.2	n.441+771_441+772delTT		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD8	ENST00000646647	c.*141_*142delAA		3_prime_UTR_variant	Exon 38 of 38		NM_001170629.2	ENSP00000495240.1

Frequencies

GnomAD3 genomes AF: 0.000108 AC: 15 AN: 138780 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000368

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000721

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00751 AC: 6784 AN: 903434 Hom.: 0 AF XY: 0.00742 AC XY: 3285 AN XY: 442454

Gnomad4 AFR exome AF: 0.0161

Gnomad4 AMR exome AF: 0.00814

Gnomad4 ASJ exome AF: 0.00637

Gnomad4 EAS exome AF: 0.00532

Gnomad4 SAS exome AF: 0.0103

Gnomad4 FIN exome AF: 0.00671

Gnomad4 NFE exome AF: 0.00715

Gnomad4 OTH exome AF: 0.00852

GnomAD4 genome AF: 0.000108 AC: 15 AN: 138810 Hom.: 0 Cov.: 31 AF XY: 0.0000894 AC XY: 6 AN XY: 67108

Gnomad4 AFR AF: 0.000367

Gnomad4 AMR AF: 0.0000720

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

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;