NM_001170629.2:c.*141_*142dupAA

Variant names:

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

Variant summary

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

The NM_001170629.2(CHD8):​c.*141_*142dupAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00080 (0 hom.)
  • Failed GnomAD Quality Control
• 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 sas. gnomad4_exome allele frequency = 0.0008 (746/931954) while in subpopulation SAS AF= 0.00139 (63/45486). AF 95% confidence interval is 0.00111. There are 0 homozygotes in gnomad4_exome. There are 348 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAdExome4 at 746 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 138824 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000800 AC: 746 AN: 931954 Hom.: 0 Cov.: 0 AF XY: 0.000762 AC XY: 348 AN XY: 456568

Gnomad4 AFR exome AF: 0.000364

Gnomad4 AMR exome AF: 0.000364

Gnomad4 ASJ exome AF: 0.000324

Gnomad4 EAS exome AF: 0.000532

Gnomad4 SAS exome AF: 0.00139

Gnomad4 FIN exome AF: 0.000499

Gnomad4 NFE exome AF: 0.000844

Gnomad4 OTH exome AF: 0.000346

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 138854 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 67124

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

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

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-21853629;