NM_000892.5:c.202A>C

Variant names:

• chr4-186232270-A-C
• NM_000892.5:c.202A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000892.5(KLKB1):​c.202A>C​(p.Ile68Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KLKB1 NM_000892.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24

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]

ENSG00000290316 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.106966496).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLKB1	NM_000892.5	c.202A>C	p.Ile68Leu	missense_variant	Exon 3 of 15	ENST00000264690.11	NP_000883.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLKB1	ENST00000264690.11	c.202A>C	p.Ile68Leu	missense_variant	Exon 3 of 15	1	NM_000892.5	ENSP00000264690.6
ENSG00000290316	ENST00000511608.5	c.343A>C	p.Ile115Leu	missense_variant	Exon 3 of 15	5		ENSP00000426629.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461766 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727184

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	2.9
DANN	Benign	0.91
DEOGEN2	Benign	0.29	T;.;T;T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.59	T;.;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.30	N;N;N;.
REVEL	Benign	0.088
Sift	Benign	0.079	T;D;T;.
Sift4G	Benign	0.12	T;T;T;T
Vest4		0.22, 0.22
MutPred		0.31		Loss of catalytic residue at I68 (P = 0.0191);Loss of catalytic residue at I68 (P = 0.0191);.;.;
MVP		0.55
MPC		0.11
ClinPred		0.096	T
GERP RS		1.4
gMVP		0.39

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-187153424;