rs1912826

chr4-186228386-G-Achr4-186228386-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000892.5(KLKB1):c.58+133G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 679,390 control chromosomes in the GnomAD database, including 95,899 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.56 (24245 hom., cov: 31)
  • Exomes 𝑓: 0.52 (71654 hom.)
• Consequence: KLKB1 NM_000892.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.140

Genes affected

KLKB1 (HGNC:6371): (kallikrein B1) This gene encodes a glycoprotein that participates in the surface-dependent activation of blood coagulation, fibrinolysis, kinin generation and inflammation. The encoded preproprotein present in plasma as a non-covalent complex with high molecular weight kininogen undergoes proteolytic processing mediated by activated coagulation factor XII to generate a disulfide-linked, heterodimeric serine protease comprised of heavy and light chains. Certain mutations in this gene cause prekallikrein deficiency. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 4-186228386-G-A is Benign according to our data. Variant chr4-186228386-G-A is described in ClinVar as [Benign]. Clinvar id is 1263748.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLKB1	NM_000892.5	c.58+133G>A		intron_variant		ENST00000264690.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLKB1	ENST00000264690.11	c.58+133G>A		intron_variant		1	NM_000892.5	P1

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85076 AN: 151754 Hom.: 24215 Cov.: 31

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.554

GnomAD4 exome AF: 0.515 AC: 271689 AN: 527518 Hom.: 71654 AF XY: 0.504 AC XY: 143664 AN XY: 284818

Gnomad4 AFR exome AF: 0.650

Gnomad4 AMR exome AF: 0.615

Gnomad4 ASJ exome AF: 0.436

Gnomad4 EAS exome AF: 0.639

Gnomad4 SAS exome AF: 0.390

Gnomad4 FIN exome AF: 0.576

Gnomad4 NFE exome AF: 0.506

Gnomad4 OTH exome AF: 0.530

GnomAD4 genome AF: 0.561 AC: 85158 AN: 151872 Hom.: 24245 Cov.: 31 AF XY: 0.560 AC XY: 41588 AN XY: 74210

Gnomad4 AFR AF: 0.645

Gnomad4 AMR AF: 0.577

Gnomad4 ASJ AF: 0.444

Gnomad4 EAS AF: 0.680

Gnomad4 SAS AF: 0.396

Gnomad4 FIN AF: 0.582

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.555

Alfa AF: 0.504 Hom.: 38419

Bravo AF: 0.570

Asia WGS AF: 0.524 AC: 1823 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.51
Dann	Benign	0.44

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: rs1912826; hg19: chr4-187149540; COSMIC: COSV52994575;