19-50908132-T-C

Position:

• chr19-50908132-T-C

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.612+227A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 596,418 control chromosomes in the GnomAD database, including 32,834 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (11705 hom., cov: 31)
  • Exomes 𝑓: 0.30 (21129 hom.)
• Consequence: KLK4 NM_004917.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.39

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=-0.88).
• BP6: Variant 19-50908132-T-C is Benign according to our data. Variant chr19-50908132-T-C is described in ClinVar as [Benign]. Clinvar id is 1279596.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK4	NM_004917.5	c.612+227A>G		intron_variant		ENST00000324041.6	NP_004908.4
KLK4	NM_001302961.2	c.327+227A>G		intron_variant			NP_001289890.1
KLK4	NR_126566.2	n.601+227A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK4	ENST00000324041.6	c.612+227A>G		intron_variant		1	NM_004917.5	ENSP00000326159.1

Frequencies

GnomAD3 genomes AF: 0.369 AC: 55999 AN: 151890 Hom.: 11672 Cov.: 31

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.389

GnomAD4 exome AF: 0.301 AC: 133832 AN: 444410 Hom.: 21129 Cov.: 5 AF XY: 0.300 AC XY: 70110 AN XY: 233816

Gnomad4 AFR exome AF: 0.571

Gnomad4 AMR exome AF: 0.258

Gnomad4 ASJ exome AF: 0.272

Gnomad4 EAS exome AF: 0.168

Gnomad4 SAS exome AF: 0.284

Gnomad4 FIN exome AF: 0.316

Gnomad4 NFE exome AF: 0.306

Gnomad4 OTH exome AF: 0.322

GnomAD4 genome AF: 0.369 AC: 56076 AN: 152008 Hom.: 11705 Cov.: 31 AF XY: 0.363 AC XY: 26992 AN XY: 74320

Gnomad4 AFR AF: 0.569

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.385

Alfa AF: 0.312 Hom.: 3817

Bravo AF: 0.378

Asia WGS AF: 0.236 AC: 823 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	clinical testing	GeneDx	Jun 19, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.3
DANN	Benign	0.68

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: rs2979451; hg19: chr19-51411388;