rs11781886

chr8-23682904-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
NKX3-1	NM_006167.4	c.-15G>A		5_prime_UTR_variant	1/2	ENST00000380871.5
LOC107986930	XR_001745842.2	n.1312+14154C>T		intron_variant, non_coding_transcript_variant
NKX3-1	NR_046072.2	n.35G>A		splice_region_variant, non_coding_transcript_exon_variant	1/2
NKX3-1	NM_001256339.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NKX3-1	ENST00000380871.5	c.-15G>A		5_prime_UTR_variant	1/2	1	NM_006167.4	P2
NKX3-1	ENST00000523261.1			upstream_gene_variant		1		A2

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

GnomAD3 exomes AF: 0.720 AC: 34082 AN: 47312 Hom.: 12282 AF XY: 0.724 AC XY: 19104 AN XY: 26378

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 SAS exome AF: 0.686

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

Gnomad4 AFR exome AF: 0.690

Gnomad4 AMR exome AF: 0.682

Gnomad4 ASJ exome AF: 0.719

Gnomad4 EAS exome AF: 0.662

Gnomad4 SAS exome AF: 0.675

Gnomad4 FIN exome AF: 0.645

Gnomad4 NFE exome AF: 0.760

Gnomad4 OTH exome AF: 0.744

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

Gnomad4 AFR AF: 0.698

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.719

Gnomad4 EAS AF: 0.715

Gnomad4 SAS AF: 0.673

Gnomad4 FIN AF: 0.620

Gnomad4 NFE AF: 0.753

Gnomad4 OTH AF: 0.722

Alfa AF: 0.741 Hom.: 31127

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

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: rs11781886; hg19: chr8-23540417; COSMIC: COSV66512040; COSMIC: COSV66512040;