14-21385470-AT-A

Position:

• chr14-21385470-AT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001170629.2(CHD8):​c.*142del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0472 in 138,474 control chromosomes in the GnomAD database, including 417 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.047 (417 hom., cov: 31)
  • Exomes 𝑓: 0.28 (25 hom.)
  • Failed GnomAD Quality Control
• Consequence: CHD8 NM_001170629.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 14-21385470-AT-A is Benign according to our data. Variant chr14-21385470-AT-A is described in ClinVar as [Benign]. Clinvar id is 1183346.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHD8	NM_001170629.2	c.*142del		3_prime_UTR_variant	38/38	ENST00000646647.2
LOC107984643	XR_001750627.2	n.441+772del		intron_variant, non_coding_transcript_variant
CHD8	NM_020920.4	c.*142del		3_prime_UTR_variant	38/38

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHD8	ENST00000646647.2	c.*142del		3_prime_UTR_variant	38/38		NM_001170629.2	P3

Frequencies

GnomAD3 genomes AF: 0.0471 AC: 6517 AN: 138444 Hom.: 415 Cov.: 31

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0220

Gnomad ASJ AF: 0.0128

Gnomad EAS AF: 0.00205

Gnomad SAS AF: 0.00137

Gnomad FIN AF: 0.0115

Gnomad MID AF: 0.0135

Gnomad NFE AF: 0.00434

Gnomad OTH AF: 0.0439

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.281 AC: 237779 AN: 845428 Hom.: 25 Cov.: 0 AF XY: 0.283 AC XY: 116926 AN XY: 412990

Gnomad4 AFR exome AF: 0.353

Gnomad4 AMR exome AF: 0.325

Gnomad4 ASJ exome AF: 0.316

Gnomad4 EAS exome AF: 0.325

Gnomad4 SAS exome AF: 0.277

Gnomad4 FIN exome AF: 0.319

Gnomad4 NFE exome AF: 0.274

Gnomad4 OTH exome AF: 0.294

GnomAD4 genome AF: 0.0472 AC: 6536 AN: 138474 Hom.: 417 Cov.: 31 AF XY: 0.0470 AC XY: 3148 AN XY: 66910

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.0219

Gnomad4 ASJ AF: 0.0128

Gnomad4 EAS AF: 0.00205

Gnomad4 SAS AF: 0.00138

Gnomad4 FIN AF: 0.0115

Gnomad4 NFE AF: 0.00436

Gnomad4 OTH AF: 0.0442

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 20, 2019

- -

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;