rs13037749

Positions:

• chr20-41435919-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032221.5(CHD6):​c.4068+1355T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0496 in 152,286 control chromosomes in the GnomAD database, including 272 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.050 (272 hom., cov: 32)
• Consequence: CHD6 NM_032221.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD6	NM_032221.5	c.4068+1355T>C		intron_variant		ENST00000373233.8	NP_115597.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHD6	ENST00000373233.8	c.4068+1355T>C		intron_variant		1	NM_032221.5	ENSP00000362330	P1
CHD6	ENST00000440697.5	c.*46+1355T>C		intron_variant		5		ENSP00000404637

Frequencies

GnomAD3 genomes AF: 0.0497 AC: 7561 AN: 152168 Hom.: 273 Cov.: 32

Gnomad AFR AF: 0.0125

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.0416

Gnomad ASJ AF: 0.0977

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0320

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0727

Gnomad OTH AF: 0.0554

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0496 AC: 7558 AN: 152286 Hom.: 272 Cov.: 32 AF XY: 0.0489 AC XY: 3641 AN XY: 74462

Gnomad4 AFR AF: 0.0125

Gnomad4 AMR AF: 0.0415

Gnomad4 ASJ AF: 0.0977

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.0320

Gnomad4 NFE AF: 0.0727

Gnomad4 OTH AF: 0.0544

Alfa AF: 0.0701 Hom.: 376

Bravo AF: 0.0465

Asia WGS AF: 0.0450 AC: 157 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.51
DANN	Benign	0.42

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: rs13037749; hg19: chr20-40064559;