rs11781886

Variant names:

• chr8-23682904-C-T
• rs11781886
• NM_006167.4:c.-15G>A

Variant summary

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

The NM_006167.4(NKX3-1):​c.-15G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 1,430,684 control chromosomes in the GnomAD database, including 396,762 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 0.72 (39199 hom., cov: 32)
  • Exomes 𝑓: 0.75 (357563 hom.)
• Consequence: NKX3-1 NM_006167.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79
• Publications: 31 publications found

Genes affected

NKX3-1 (HGNC:7838): (NK3 homeobox 1) This gene encodes a homeobox-containing transcription factor. This transcription factor functions as a negative regulator of epithelial cell growth in prostate tissue. Aberrant expression of this gene is associated with prostate tumor progression. Alternate splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jan 2012]

LOC107986930 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NKX3-1	NM_006167.4	c.-15G>A		5_prime_UTR_variant	Exon 1 of 2	ENST00000380871.5	NP_006158.2
NKX3-1	NR_046072.2	n.35G>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 1 of 2
LOC107986930	XR_001745842.2	n.1312+14154C>T		intron_variant	Intron 3 of 4
NKX3-1	NM_001256339.1	c.-15G>A		upstream_gene_variant			NP_001243268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NKX3-1	ENST00000380871.5	c.-15G>A		5_prime_UTR_variant	Exon 1 of 2	1	NM_006167.4	ENSP00000370253.4
NKX3-1	ENST00000523261.1	c.-15G>A		upstream_gene_variant		1		ENSP00000429729.1

Frequencies

GnomAD3 genomes AF: 0.717 AC: 108811 AN: 151756 Hom.: 39174 Cov.: 32

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.809

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.725

GnomAD2 exomes AF: 0.720 AC: 34082 AN: 47312 AF XY: 0.724

Gnomad AFR exome AF: 0.724

Gnomad AMR exome AF: 0.684

Gnomad ASJ exome AF: 0.728

Gnomad EAS exome AF: 0.743

Gnomad FIN exome AF: 0.643

Gnomad NFE exome AF: 0.768

Gnomad OTH exome AF: 0.729

GnomAD4 exome AF: 0.747 AC: 955240 AN: 1278818 Hom.: 357563 Cov.: 65 AF XY: 0.746 AC XY: 465788 AN XY: 624684

African (AFR) AF: 0.690 AC: 17712 AN: 25664

American (AMR) AF: 0.682 AC: 15512 AN: 22730

Ashkenazi Jewish (ASJ) AF: 0.719 AC: 14102 AN: 19600

East Asian (EAS) AF: 0.662 AC: 19152 AN: 28922

South Asian (SAS) AF: 0.675 AC: 43273 AN: 64062

European-Finnish (FIN) AF: 0.645 AC: 19879 AN: 30810

Middle Eastern (MID) AF: 0.733 AC: 2764 AN: 3772

European-Non Finnish (NFE) AF: 0.760 AC: 783359 AN: 1030206

Other (OTH) AF: 0.744 AC: 39487 AN: 53052

GnomAD4 genome AF: 0.717 AC: 108888 AN: 151866 Hom.: 39199 Cov.: 32 AF XY: 0.709 AC XY: 52610 AN XY: 74242

African (AFR) AF: 0.698 AC: 28931 AN: 41442

American (AMR) AF: 0.691 AC: 10566 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.719 AC: 2496 AN: 3470

East Asian (EAS) AF: 0.715 AC: 3643 AN: 5094

South Asian (SAS) AF: 0.673 AC: 3247 AN: 4824

European-Finnish (FIN) AF: 0.620 AC: 6553 AN: 10570

Middle Eastern (MID) AF: 0.801 AC: 234 AN: 292

European-Non Finnish (NFE) AF: 0.753 AC: 51100 AN: 67864

Other (OTH) AF: 0.722 AC: 1524 AN: 2110

Alfa AF: 0.740 Hom.: 38624

Bravo AF: 0.724

Asia WGS AF: 0.670 AC: 2322 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.3
DANN	Benign	0.90
PhyloP100		-1.8
PromoterAI		-0.31	Neutral
Mutation Taster		=300/0	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: rs11781886; hg19: chr8-23540417; COSMIC: COSV66512040; COSMIC: COSV66512040;