20-41412230-G-A

Position:

• chr20-41412230-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000373233.8(CHD6):​c.7165C>T​(p.Arg2389Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,614,072 control chromosomes in the GnomAD database, including 200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0095 (22 hom., cov: 33)
  • Exomes 𝑓: 0.010 (178 hom.)
• Consequence: CHD6 ENST00000373233.8 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 7.50

Genes affected

CHD6 (HGNC:19057): (chromodomain helicase DNA binding protein 6) This gene encodes a member of the SNF2/RAD54 helicase protein family. The encoded protein contains two chromodomains, a helicase domain, and an ATPase domain. Several multi-subunit protein complexes remodel chromatin to allow patterns of cell type-specific gene expression, and the encoded protein is thought to be a core member of one or more of these chromatin remodeling complexes. The encoded protein may function as a transcriptional repressor and is involved in the cellular repression of influenza virus replication. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006835401).
• BP6: Variant 20-41412230-G-A is Benign according to our data. Variant chr20-41412230-G-A is described in ClinVar as [Benign]. Clinvar id is 218816.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-41412230-G-A is described in Lovd as [Benign].
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD6	NM_032221.5	c.7165C>T	p.Arg2389Cys	missense_variant	36/37	ENST00000373233.8	NP_115597.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHD6	ENST00000373233.8	c.7165C>T	p.Arg2389Cys	missense_variant	36/37	1	NM_032221.5	ENSP00000362330	P1
CHD6	ENST00000480022.1	n.1776C>T		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes AF: 0.00948 AC: 1443 AN: 152198 Hom.: 22 Cov.: 33

Gnomad AFR AF: 0.00234

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0326

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.00423

Gnomad SAS AF: 0.00434

Gnomad FIN AF: 0.0115

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00883

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.0170 AC: 4265 AN: 251458 Hom.: 118 AF XY: 0.0148 AC XY: 2017 AN XY: 135908

Gnomad AFR exome AF: 0.00191

Gnomad AMR exome AF: 0.0728

Gnomad ASJ exome AF: 0.0160

Gnomad EAS exome AF: 0.00250

Gnomad SAS exome AF: 0.00562

Gnomad FIN exome AF: 0.0134

Gnomad NFE exome AF: 0.00836

Gnomad OTH exome AF: 0.0156

GnomAD4 exome AF: 0.0103 AC: 15129 AN: 1461756 Hom.: 178 Cov.: 30 AF XY: 0.00997 AC XY: 7250 AN XY: 727202

Gnomad4 AFR exome AF: 0.00194

Gnomad4 AMR exome AF: 0.0687

Gnomad4 ASJ exome AF: 0.0148

Gnomad4 EAS exome AF: 0.00464

Gnomad4 SAS exome AF: 0.00588

Gnomad4 FIN exome AF: 0.0132

Gnomad4 NFE exome AF: 0.00865

Gnomad4 OTH exome AF: 0.00941

GnomAD4 genome AF: 0.00950 AC: 1447 AN: 152316 Hom.: 22 Cov.: 33 AF XY: 0.00923 AC XY: 687 AN XY: 74462

Gnomad4 AFR AF: 0.00233

Gnomad4 AMR AF: 0.0329

Gnomad4 ASJ AF: 0.0161

Gnomad4 EAS AF: 0.00386

Gnomad4 SAS AF: 0.00435

Gnomad4 FIN AF: 0.0115

Gnomad4 NFE AF: 0.00885

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00882 Hom.: 8

Bravo AF: 0.0118

TwinsUK AF: 0.00809 AC: 30

ALSPAC AF: 0.00727 AC: 28

ESP6500AA AF: 0.00250 AC: 11

ESP6500EA AF: 0.00802 AC: 69

ExAC AF: 0.0144 AC: 1753

Asia WGS AF: 0.00635 AC: 22 AN: 3478

EpiCase AF: 0.00862

EpiControl AF: 0.00711

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

May 05, 2015

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.72	D
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D
MetaRNN	Benign	0.0068	T
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.3	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.30
MPC		0.75
ClinPred		0.021	T
GERP RS		5.2
Varity_R		0.53
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs61752057; hg19: chr20-40040870;