19-50907142-G-A

Position:

• chr19-50907142-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004917.5(KLK4):​c.613-56C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0343 in 1,577,026 control chromosomes in the GnomAD database, including 1,188 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (124 hom., cov: 32)
  • Exomes 𝑓: 0.035 (1064 hom.)
• Consequence: KLK4 NM_004917.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.352

Genes affected

KLK4 (HGNC:6365): (kallikrein related peptidase 4) 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. In some tissues its expression is hormonally regulated. The expression pattern of a similar mouse protein in murine developing teeth supports a role for the protein in the degradation of enamel proteins. Several transcript variants encoding different proteins have been found for this gene. [provided by RefSeq, Dec 2014]

KLK4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 19-50907142-G-A is Benign according to our data. Variant chr19-50907142-G-A is described in ClinVar as [Benign]. Clinvar id is 1288569.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK4	NM_004917.5	c.613-56C>T		intron_variant		ENST00000324041.6	NP_004908.4
KLK4	NM_001302961.2	c.328-56C>T		intron_variant			NP_001289890.1
KLK4	NR_126566.2	n.602-56C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK4	ENST00000324041.6	c.613-56C>T		intron_variant		1	NM_004917.5	ENSP00000326159.1

Frequencies

GnomAD3 genomes AF: 0.0305 AC: 4643 AN: 152168 Hom.: 123 Cov.: 32

Gnomad AFR AF: 0.00746

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0710

Gnomad ASJ AF: 0.0461

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0205

Gnomad FIN AF: 0.0660

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0325

Gnomad OTH AF: 0.0277

GnomAD4 exome AF: 0.0347 AC: 49469 AN: 1424740 Hom.: 1064 AF XY: 0.0339 AC XY: 24078 AN XY: 711004

Gnomad4 AFR exome AF: 0.00581

Gnomad4 AMR exome AF: 0.0956

Gnomad4 ASJ exome AF: 0.0409

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0213

Gnomad4 FIN exome AF: 0.0558

Gnomad4 NFE exome AF: 0.0346

Gnomad4 OTH exome AF: 0.0307

GnomAD4 genome AF: 0.0305 AC: 4648 AN: 152286 Hom.: 124 Cov.: 32 AF XY: 0.0328 AC XY: 2439 AN XY: 74470

Gnomad4 AFR AF: 0.00743

Gnomad4 AMR AF: 0.0714

Gnomad4 ASJ AF: 0.0461

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0203

Gnomad4 FIN AF: 0.0660

Gnomad4 NFE AF: 0.0324

Gnomad4 OTH AF: 0.0274

Alfa AF: 0.0143 Hom.: 4

Bravo AF: 0.0300

Asia WGS AF: 0.0110 AC: 39 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 20, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	0.18

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: rs198965; hg19: chr19-51410398;