19-50907860-T-C

Position:

• chr19-50907860-T-C

Variant summary

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

The NM_004917.5(KLK4):​c.612+499A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 234,838 control chromosomes in the GnomAD database, including 27,438 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 0.49 (18730 hom., cov: 33)
  • Exomes 𝑓: 0.44 (8708 hom.)
• Consequence: KLK4 NM_004917.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.433

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK4	NM_004917.5	c.612+499A>G		intron_variant		ENST00000324041.6	NP_004908.4
KLK4	NM_001302961.2	c.327+499A>G		intron_variant			NP_001289890.1
KLK4	NR_126566.2	n.601+499A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK4	ENST00000324041.6	c.612+499A>G		intron_variant		1	NM_004917.5	ENSP00000326159.1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74274 AN: 151938 Hom.: 18712 Cov.: 33

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.490

GnomAD4 exome AF: 0.436 AC: 36065 AN: 82782 Hom.: 8708 AF XY: 0.426 AC XY: 18229 AN XY: 42798

Gnomad4 AFR exome AF: 0.541

Gnomad4 AMR exome AF: 0.474

Gnomad4 ASJ exome AF: 0.567

Gnomad4 EAS exome AF: 0.114

Gnomad4 SAS exome AF: 0.311

Gnomad4 FIN exome AF: 0.464

Gnomad4 NFE exome AF: 0.473

Gnomad4 OTH exome AF: 0.472

GnomAD4 genome AF: 0.489 AC: 74335 AN: 152056 Hom.: 18730 Cov.: 33 AF XY: 0.487 AC XY: 36189 AN XY: 74332

Gnomad4 AFR AF: 0.554

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.550

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.501

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.486

Alfa AF: 0.477 Hom.: 34980

Bravo AF: 0.493

Asia WGS AF: 0.228 AC: 797 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.1
DANN	Benign	0.56

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: rs1654553; hg19: chr19-51411116;