rs2235091

Positions:

• chr19-50907215-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004917.5(KLK4):​c.613-129T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 933,878 control chromosomes in the GnomAD database, including 63,255 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.37 (10907 hom., cov: 30)
  • Exomes 𝑓: 0.36 (52348 hom.)
• Consequence: KLK4 NM_004917.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.199

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 19-50907215-A-G is Benign according to our data. Variant chr19-50907215-A-G is described in ClinVar as [Benign]. Clinvar id is 1261892.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK4	NM_004917.5	c.613-129T>C		intron_variant		ENST00000324041.6	NP_004908.4
KLK4	NM_001302961.2	c.328-129T>C		intron_variant			NP_001289890.1
KLK4	NR_126566.2	n.602-129T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK4	ENST00000324041.6	c.613-129T>C		intron_variant		1	NM_004917.5	ENSP00000326159.1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56831 AN: 151784 Hom.: 10894 Cov.: 30

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.393

GnomAD4 exome AF: 0.359 AC: 280948 AN: 781976 Hom.: 52348 AF XY: 0.363 AC XY: 148597 AN XY: 409128

Gnomad4 AFR exome AF: 0.428

Gnomad4 AMR exome AF: 0.313

Gnomad4 ASJ exome AF: 0.325

Gnomad4 EAS exome AF: 0.179

Gnomad4 SAS exome AF: 0.425

Gnomad4 FIN exome AF: 0.345

Gnomad4 NFE exome AF: 0.365

Gnomad4 OTH exome AF: 0.364

GnomAD4 genome AF: 0.374 AC: 56875 AN: 151902 Hom.: 10907 Cov.: 30 AF XY: 0.371 AC XY: 27524 AN XY: 74256

Gnomad4 AFR AF: 0.424

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.388

Alfa AF: 0.374 Hom.: 19883

Bravo AF: 0.377

Asia WGS AF: 0.306 AC: 1065 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.1
DANN	Benign	0.72

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: rs2235091; hg19: chr19-51410471;