rs9458849

chr6-163522193-A-G

Variant summary

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

The NM_006775.3(QKI):c.403-12789A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0797 in 152,238 control chromosomes in the GnomAD database, including 555 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 0.080 (555 hom., cov: 32)
• Consequence: QKI NM_006775.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02

Genes affected

QKI (HGNC:21100): (QKI, KH domain containing RNA binding) The protein encoded by this gene is an RNA-binding protein that regulates pre-mRNA splicing, export of mRNAs from the nucleus, protein translation, and mRNA stability. The encoded protein is involved in myelinization and oligodendrocyte differentiation and may play a role in schizophrenia. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
QKI	NM_006775.3	c.403-12789A>G		intron_variant		ENST00000361752.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
QKI	ENST00000361752.8	c.403-12789A>G		intron_variant		1	NM_006775.3	P3

Frequencies

GnomAD3 genomes AF: 0.0798 AC: 12132 AN: 152120 Hom.: 555 Cov.: 32

Gnomad AFR AF: 0.0992

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.0689

Gnomad ASJ AF: 0.0899

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0615

Gnomad FIN AF: 0.0444

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0818

Gnomad OTH AF: 0.0813

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

GnomAD4 genome AF: 0.0797 AC: 12133 AN: 152238 Hom.: 555 Cov.: 32 AF XY: 0.0776 AC XY: 5781 AN XY: 74452

Gnomad4 AFR AF: 0.0990

Gnomad4 AMR AF: 0.0688

Gnomad4 ASJ AF: 0.0899

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0614

Gnomad4 FIN AF: 0.0444

Gnomad4 NFE AF: 0.0818

Gnomad4 OTH AF: 0.0799

Alfa AF: 0.0197 Hom.: 6

Bravo AF: 0.0820

Asia WGS AF: 0.0300 AC: 105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.70
Dann	Benign	0.57

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: rs9458849; hg19: chr6-163943225;