Variant 14-21385465-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001170629.2(CHD8):c.*148C>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00144 in 1,201,374 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 8 hom. )

Consequence

CHD8
NM_001170629.2 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.56

Variant links:

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]

CHD8 links:

LOC107984643 (HGNC:):

LOC107984643 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 14-21385465-G-A is Benign according to our data. Variant chr14-21385465-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1194978.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00228 (345/151398) while in subpopulation NFE AF= 0.00122 (83/67966). AF 95% confidence interval is 0.00101. There are 6 homozygotes in gnomad4. There are 236 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 345 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
CHD8	NM_001170629.2 linkuse as main transcript	c.*148C>T	3_prime_UTR_variant	38/38	ENST00000646647.2
LOC107984643	XR_001750627.2 linkuse as main transcript	n.441+752G>A	intron_variant, non_coding_transcript_variant
CHD8	NM_020920.4 linkuse as main transcript	c.*148C>T	3_prime_UTR_variant	38/38

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHD8	ENST00000646647.2 linkuse as main transcript	c.*148C>T		3_prime_UTR_variant	38/38		NM_001170629.2	P3	Q9HCK8-1

Frequencies

GnomAD3 genomes

AF:

0.00228

AC:

345

AN:

151284

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000172

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000788

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0229

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00122

Gnomad OTH

AF:

0.000480

GnomAD4 exome

AF:

0.00131

AC:

1379

AN:

1049976

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

669

AN XY:

515050

show subpopulations

Gnomad4 AFR exome

AF:

0.0000837

Gnomad4 AMR exome

AF:

0.000370

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000367

Gnomad4 FIN exome

AF:

0.0151

Gnomad4 NFE exome

AF:

0.00106

Gnomad4 OTH exome

AF:

0.000810

GnomAD4 genome

AF:

0.00228

AC:

345

AN:

151398

Hom.:

Cov.:

AF XY:

0.00319

AC XY:

236

AN XY:

73998

show subpopulations

Gnomad4 AFR

AF:

0.000171

Gnomad4 AMR

AF:

0.000787

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0229

Gnomad4 NFE

AF:

0.00122

Gnomad4 OTH

AF:

0.000475

Alfa

AF:

0.00164

Hom.:

Bravo

AF:

0.000480

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 06, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over