6-163454517-C-G

Variant names:

• chr6-163454517-C-G
• rs4709716
• NM_006775.3:c.143-762C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006775.3(QKI):​c.143-762C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 151,952 control chromosomes in the GnomAD database, including 17,320 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 0.44 (17320 hom., cov: 31)
• Consequence: QKI NM_006775.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
QKI	NM_006775.3	c.143-762C>G		intron_variant	Intron 1 of 7	ENST00000361752.8	NP_006766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
QKI	ENST00000361752.8	c.143-762C>G		intron_variant	Intron 1 of 7	1	NM_006775.3	ENSP00000355094.3

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67431 AN: 151834 Hom.: 17317 Cov.: 31

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.444 AC: 67440 AN: 151952 Hom.: 17320 Cov.: 31 AF XY: 0.451 AC XY: 33477 AN XY: 74244

African (AFR) AF: 0.173 AC: 7188 AN: 41448

American (AMR) AF: 0.532 AC: 8119 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1843 AN: 3470

East Asian (EAS) AF: 0.717 AC: 3703 AN: 5164

South Asian (SAS) AF: 0.524 AC: 2521 AN: 4810

European-Finnish (FIN) AF: 0.615 AC: 6486 AN: 10546

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.531 AC: 36077 AN: 67934

Other (OTH) AF: 0.461 AC: 973 AN: 2110

Alfa AF: 0.480 Hom.: 2360

Bravo AF: 0.426

Asia WGS AF: 0.601 AC: 2089 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.3
DANN	Benign	0.64
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4709716; hg19: chr6-163875549;