rs7772756

Positions:

• chr6-163423014-C-A
• chr6-163423014-C-G
• chr6-163423014-C-T

Variant summary

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

The NM_006775.3(QKI):​c.142+7679C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,146 control chromosomes in the GnomAD database, including 2,469 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 0.16 (2469 hom., cov: 33)
  • Exomes 𝑓: 0.083 (0 hom.)
• Consequence: QKI NM_006775.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.973

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
QKI	NM_006775.3	c.142+7679C>A		intron_variant		ENST00000361752.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
QKI	ENST00000361752.8	c.142+7679C>A		intron_variant		1	NM_006775.3	P3

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24998 AN: 152016 Hom.: 2465 Cov.: 33

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.190

GnomAD4 exome AF: 0.0833 AC: 1 AN: 12 Hom.: 0 AF XY: 0.0833 AC XY: 1 AN XY: 12

Gnomad4 NFE exome AF: 0.0833

GnomAD4 genome AF: 0.164 AC: 25003 AN: 152134 Hom.: 2469 Cov.: 33 AF XY: 0.168 AC XY: 12470 AN XY: 74358

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.259

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.188

Alfa AF: 0.0710 Hom.: 93

Bravo AF: 0.177

Asia WGS AF: 0.203 AC: 706 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.94
DANN	Benign	0.39

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: rs7772756; hg19: chr6-163844046;