rs2250066

Positions:

• chr19-51025863-C-T

Variant summary

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

The NM_001136032.3(KLK11):​c.-35-197G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 435,576 control chromosomes in the GnomAD database, including 5,936 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 0.18 (3176 hom., cov: 31)
  • Exomes 𝑓: 0.13 (2760 hom.)
• Consequence: KLK11 NM_001136032.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67

Genes affected

KLK11 (HGNC:6359): (kallikrein related peptidase 11) Kallikreins are a subgroup of serine proteases having diverse physiological functions. Growing evidence suggests that many kallikreins are implicated in carcinogenesis and some have potential as novel cancer and other disease biomarkers. This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. Alternate splicing and the use of alternate promoters results in multiple transcript variants encoding distinct isoforms which are differentially expressed. [provided by RefSeq, Dec 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK11	NM_001136032.3	c.-35-197G>A		intron_variant		ENST00000453757.8	NP_001129504.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK11	ENST00000453757.8	c.-35-197G>A		intron_variant		1	NM_001136032.3	ENSP00000413958	P1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27727 AN: 151986 Hom.: 3164 Cov.: 31

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0821

Gnomad EAS AF: 0.0422

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.0954

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.154

GnomAD4 exome AF: 0.132 AC: 37434 AN: 283472 Hom.: 2760 Cov.: 0 AF XY: 0.132 AC XY: 19403 AN XY: 146964

Gnomad4 AFR exome AF: 0.320

Gnomad4 AMR exome AF: 0.0911

Gnomad4 ASJ exome AF: 0.0782

Gnomad4 EAS exome AF: 0.0609

Gnomad4 SAS exome AF: 0.141

Gnomad4 FIN exome AF: 0.0901

Gnomad4 NFE exome AF: 0.142

Gnomad4 OTH exome AF: 0.142

GnomAD4 genome AF: 0.183 AC: 27778 AN: 152104 Hom.: 3176 Cov.: 31 AF XY: 0.178 AC XY: 13220 AN XY: 74346

Gnomad4 AFR AF: 0.327

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.0821

Gnomad4 EAS AF: 0.0423

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.0954

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.155

Alfa AF: 0.147 Hom.: 2337

Bravo AF: 0.187

Asia WGS AF: 0.141 AC: 492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.0
DANN	Benign	0.79

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: rs2250066; hg19: chr19-51529119;