rs2659058

Positions:

• chr19-50822850-C-T

Variant summary

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

The NM_002257.4(KLK1):​c.46+853G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 979,162 control chromosomes in the GnomAD database, including 229,176 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 0.69 (36632 hom., cov: 30)
  • Exomes 𝑓: 0.68 (192544 hom.)
• Consequence: KLK1 NM_002257.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.791

Genes affected

KLK1 (HGNC:6357): (kallikrein 1) 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. This protein is functionally conserved in its capacity to release the vasoactive peptide, Lys-bradykinin, from low molecular weight kininogen. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK1	NM_002257.4	c.46+853G>A		intron_variant		ENST00000301420.3	NP_002248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK1	ENST00000301420.3	c.46+853G>A		intron_variant		1	NM_002257.4	ENSP00000301420	P1
KLK1	ENST00000593325.5	c.122+27G>A		intron_variant, NMD_transcript_variant		2		ENSP00000472939
KLK1	ENST00000593859.5	n.85+853G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.693 AC: 105135 AN: 151740 Hom.: 36582 Cov.: 30

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.800

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.680

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.698

GnomAD3 exomes AF: 0.669 AC: 119 AN: 178 Hom.: 40 AF XY: 0.615 AC XY: 32 AN XY: 52

Gnomad AFR exome AF: 0.684

Gnomad AMR exome AF: 1.00

Gnomad ASJ exome AF: 0.750

Gnomad EAS exome AF: 0.667

Gnomad FIN exome AF: 0.500

Gnomad NFE exome AF: 0.676

Gnomad OTH exome AF: 0.571

GnomAD4 exome AF: 0.681 AC: 563722 AN: 827302 Hom.: 192544 Cov.: 17 AF XY: 0.682 AC XY: 260520 AN XY: 382264

Gnomad4 AFR exome AF: 0.687

Gnomad4 AMR exome AF: 0.723

Gnomad4 ASJ exome AF: 0.621

Gnomad4 EAS exome AF: 0.791

Gnomad4 SAS exome AF: 0.618

Gnomad4 FIN exome AF: 0.698

Gnomad4 NFE exome AF: 0.683

Gnomad4 OTH exome AF: 0.670

GnomAD4 genome AF: 0.693 AC: 105243 AN: 151860 Hom.: 36632 Cov.: 30 AF XY: 0.692 AC XY: 51336 AN XY: 74210

Gnomad4 AFR AF: 0.702

Gnomad4 AMR AF: 0.742

Gnomad4 ASJ AF: 0.633

Gnomad4 EAS AF: 0.800

Gnomad4 SAS AF: 0.633

Gnomad4 FIN AF: 0.680

Gnomad4 NFE AF: 0.679

Gnomad4 OTH AF: 0.701

Alfa AF: 0.678 Hom.: 4704

Bravo AF: 0.702

Asia WGS AF: 0.707 AC: 2457 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.0
DANN	Benign	0.50

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: rs2659058; hg19: chr19-51326106;