19-50822930-G-C

Position:

• chr19-50822930-G-C

Variant summary

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

The NM_002257.4(KLK1):​c.46+773C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 983,158 control chromosomes in the GnomAD database, including 75,299 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 0.34 (9076 hom., cov: 30)
  • Exomes 𝑓: 0.40 (66223 hom.)
• Consequence: KLK1 NM_002257.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.644

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK1	NM_002257.4	c.46+773C>G		intron_variant		ENST00000301420.3	NP_002248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK1	ENST00000301420.3	c.46+773C>G		intron_variant		1	NM_002257.4	ENSP00000301420.1
KLK1	ENST00000593325.5	n.69C>G		non_coding_transcript_exon_variant	2/6	2		ENSP00000472939.1
KLK1	ENST00000593859.5	n.85+773C>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51335 AN: 151820 Hom.: 9082 Cov.: 30

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.373

GnomAD3 exomes AF: 0.410 AC: 55 AN: 134 Hom.: 9 AF XY: 0.479 AC XY: 23 AN XY: 48

Gnomad AFR exome AF: 0.182

Gnomad AMR exome AF: 0.500

Gnomad ASJ exome AF: 0.333

Gnomad EAS exome AF: 0.200

Gnomad FIN exome AF: 0.500

Gnomad NFE exome AF: 0.500

Gnomad OTH exome AF: 0.375

GnomAD4 exome AF: 0.397 AC: 330157 AN: 831218 Hom.: 66223 Cov.: 27 AF XY: 0.398 AC XY: 152804 AN XY: 383938

Gnomad4 AFR exome AF: 0.230

Gnomad4 AMR exome AF: 0.307

Gnomad4 ASJ exome AF: 0.369

Gnomad4 EAS exome AF: 0.204

Gnomad4 SAS exome AF: 0.335

Gnomad4 FIN exome AF: 0.388

Gnomad4 NFE exome AF: 0.404

Gnomad4 OTH exome AF: 0.370

GnomAD4 genome AF: 0.338 AC: 51329 AN: 151940 Hom.: 9076 Cov.: 30 AF XY: 0.335 AC XY: 24851 AN XY: 74242

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.210

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.400

Gnomad4 OTH AF: 0.367

Alfa AF: 0.261 Hom.: 774

Bravo AF: 0.330

Asia WGS AF: 0.250 AC: 872 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	14
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs2740502; hg19: chr19-51326186;