rs4253238

Positions:

• chr4-186227233-C-T

Variant summary

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

The ENST00000511608.5(ENSG00000290316):​c.200-4894C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 152,012 control chromosomes in the GnomAD database, including 27,161 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 0.59 (27161 hom., cov: 32)
• Consequence: ENSG00000290316 ENST00000511608.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.778

Genes affected

ENSG00000290316 (HGNC:):

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLKB1	XM_017008181.2	c.-1-962C>T		intron_variant			XP_016863670.1
KLKB1	XM_047415661.1	c.-1-962C>T		intron_variant			XP_047271617.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000290316	ENST00000511608.5	c.200-4894C>T		intron_variant		5		ENSP00000426629.1
KLKB1	ENST00000428196.5	c.-149-207C>T		intron_variant		3		ENSP00000412366.1

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89291 AN: 151894 Hom.: 27110 Cov.: 32

Gnomad AFR AF: 0.741

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.584

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: 0.568

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.588 AC: 89396 AN: 152012 Hom.: 27161 Cov.: 32 AF XY: 0.587 AC XY: 43613 AN XY: 74292

Gnomad4 AFR AF: 0.742

Gnomad4 AMR AF: 0.585

Gnomad4 ASJ AF: 0.444

Gnomad4 EAS AF: 0.680

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.582

Gnomad4 NFE AF: 0.511

Gnomad4 OTH AF: 0.569

Alfa AF: 0.513 Hom.: 26702

Bravo AF: 0.600

Asia WGS AF: 0.531 AC: 1849 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.62
DANN	Benign	0.44

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4253238; hg19: chr4-187148387;