rs1054713

chr19-50820245-A-Gchr19-50820245-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002257.4(KLK1):c.405T>C(p.Asp135=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 1,613,394 control chromosomes in the GnomAD database, including 375,506 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 0.70 (37461 hom., cov: 30)
  • Exomes 𝑓: 0.68 (338045 hom.)
• Consequence: KLK1 NM_002257.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.10

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP7: Synonymous conserved (PhyloP=-5.1 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLK1	NM_002257.4	c.405T>C	p.Asp135=	synonymous_variant	3/5	ENST00000301420.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLK1	ENST00000301420.3	c.405T>C	p.Asp135=	synonymous_variant	3/5	1	NM_002257.4	P1
KLK1	ENST00000593859.5	n.444T>C		non_coding_transcript_exon_variant	3/4	2
KLK1	ENST00000596300.1	n.605T>C		non_coding_transcript_exon_variant	1/3	2
KLK1	ENST00000593325.5	c.*1214T>C		3_prime_UTR_variant, NMD_transcript_variant	4/6	2

Frequencies

GnomAD3 genomes AF: 0.700 AC: 106220 AN: 151704 Hom.: 37413 Cov.: 30

Gnomad AFR AF: 0.745

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.795

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.701

GnomAD3 exomes AF: 0.696 AC: 174911 AN: 251386 Hom.: 61547 AF XY: 0.686 AC XY: 93248 AN XY: 135858

Gnomad AFR exome AF: 0.749

Gnomad AMR exome AF: 0.806

Gnomad ASJ exome AF: 0.618

Gnomad EAS exome AF: 0.792

Gnomad SAS exome AF: 0.625

Gnomad FIN exome AF: 0.670

Gnomad NFE exome AF: 0.671

Gnomad OTH exome AF: 0.678

GnomAD4 exome AF: 0.678 AC: 991520 AN: 1461572 Hom.: 338045 Cov.: 54 AF XY: 0.676 AC XY: 491301 AN XY: 727070

Gnomad4 AFR exome AF: 0.741

Gnomad4 AMR exome AF: 0.795

Gnomad4 ASJ exome AF: 0.615

Gnomad4 EAS exome AF: 0.782

Gnomad4 SAS exome AF: 0.631

Gnomad4 FIN exome AF: 0.673

Gnomad4 NFE exome AF: 0.674

Gnomad4 OTH exome AF: 0.676

GnomAD4 genome AF: 0.700 AC: 106326 AN: 151822 Hom.: 37461 Cov.: 30 AF XY: 0.698 AC XY: 51784 AN XY: 74174

Gnomad4 AFR AF: 0.745

Gnomad4 AMR AF: 0.740

Gnomad4 ASJ AF: 0.629

Gnomad4 EAS AF: 0.795

Gnomad4 SAS AF: 0.654

Gnomad4 FIN AF: 0.663

Gnomad4 NFE AF: 0.671

Gnomad4 OTH AF: 0.704

Alfa AF: 0.667 Hom.: 44275

Bravo AF: 0.712

Asia WGS AF: 0.721 AC: 2507 AN: 3478

EpiCase AF: 0.662

EpiControl AF: 0.659

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.017
Dann	Benign	0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1054713; hg19: chr19-51323501; COSMIC: COSV56826329; COSMIC: COSV56826329;