19-50820812-C-T

Position:

• chr19-50820812-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.207-369G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0378 in 173,294 control chromosomes in the GnomAD database, including 471 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 0.043 (460 hom., cov: 28)
  • Exomes 𝑓: 0.0053 (11 hom.)
• Consequence: KLK1 NM_002257.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.62

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]

KLK1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK1	NM_002257.4	c.207-369G>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.207-369G>A		intron_variant		1	NM_002257.4	ENSP00000301420.1
KLK1	ENST00000596300.1	n.38G>A		non_coding_transcript_exon_variant	1/3	2
KLK1	ENST00000593325.5	n.*1016-369G>A		intron_variant		2		ENSP00000472939.1
KLK1	ENST00000593859.5	n.246-369G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0425 AC: 6431 AN: 151306 Hom.: 462 Cov.: 28

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0190

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000486

Gnomad OTH AF: 0.0255

GnomAD4 exome AF: 0.00526 AC: 115 AN: 21870 Hom.: 11 Cov.: 0 AF XY: 0.00502 AC XY: 56 AN XY: 11158

Gnomad4 AFR exome AF: 0.142

Gnomad4 AMR exome AF: 0.00896

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000677

Gnomad4 OTH exome AF: 0.0132

GnomAD4 genome AF: 0.0426 AC: 6444 AN: 151424 Hom.: 460 Cov.: 28 AF XY: 0.0407 AC XY: 3007 AN XY: 73946

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.0190

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000486

Gnomad4 OTH AF: 0.0252

Alfa AF: 0.0290 Hom.: 26

Bravo AF: 0.0488

Asia WGS AF: 0.00953 AC: 33 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.7
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

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: rs3212828; hg19: chr19-51324068;