rs7255024

Variant names:

• chr19-50908007-C-A
• rs7255024
• NM_004917.5:c.612+352G>T

Variant summary

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

The NM_004917.5(KLK4):​c.612+352G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0683 in 398,964 control chromosomes in the GnomAD database, including 1,195 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 0.067 (376 hom., cov: 33)
  • Exomes 𝑓: 0.069 (819 hom.)
• Consequence: KLK4 NM_004917.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.645

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK4	NM_004917.5	c.612+352G>T		intron_variant	Intron 5 of 5	ENST00000324041.6	NP_004908.4
KLK4	NM_001302961.2	c.327+352G>T		intron_variant	Intron 4 of 4		NP_001289890.1
KLK4	NR_126566.2	n.601+352G>T		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK4	ENST00000324041.6	c.612+352G>T		intron_variant	Intron 5 of 5	1	NM_004917.5	ENSP00000326159.1

Frequencies

GnomAD3 genomes AF: 0.0672 AC: 10216 AN: 152060 Hom.: 376 Cov.: 33

Gnomad AFR AF: 0.0788

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.0739

Gnomad ASJ AF: 0.0715

Gnomad EAS AF: 0.0256

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.0270

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0627

Gnomad OTH AF: 0.0532

GnomAD4 exome AF: 0.0690 AC: 17026 AN: 246786 Hom.: 819 Cov.: 0 AF XY: 0.0752 AC XY: 9864 AN XY: 131152

Gnomad4 AFR exome AF: 0.0739

Gnomad4 AMR exome AF: 0.0732

Gnomad4 ASJ exome AF: 0.0721

Gnomad4 EAS exome AF: 0.0165

Gnomad4 SAS exome AF: 0.136

Gnomad4 FIN exome AF: 0.0330

Gnomad4 NFE exome AF: 0.0595

Gnomad4 OTH exome AF: 0.0585

GnomAD4 genome AF: 0.0672 AC: 10226 AN: 152178 Hom.: 376 Cov.: 33 AF XY: 0.0677 AC XY: 5040 AN XY: 74406

Gnomad4 AFR AF: 0.0786

Gnomad4 AMR AF: 0.0741

Gnomad4 ASJ AF: 0.0715

Gnomad4 EAS AF: 0.0255

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.0270

Gnomad4 NFE AF: 0.0628

Gnomad4 OTH AF: 0.0521

Alfa AF: 0.0647 Hom.: 51

Bravo AF: 0.0689

Asia WGS AF: 0.0870 AC: 305 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.80
DANN	Benign	0.81

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: rs7255024; hg19: chr19-51411263;