rs1654556

chr19-50906547-C-T

Variant summary

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

The NM_004917.5(KLK4):c.*387G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 237,110 control chromosomes in the GnomAD database, including 85,821 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 0.85 (41152 hom., cov: 14)
  • Exomes 𝑓: 0.83 (44669 hom.)
• Consequence: KLK4 NM_004917.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLK4	NM_004917.5	c.*387G>A		3_prime_UTR_variant	6/6	ENST00000324041.6
KLK4	NM_001302961.2	c.*387G>A		3_prime_UTR_variant	5/5
KLK4	NR_126566.2	n.1141G>A		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLK4	ENST00000324041.6	c.*387G>A		3_prime_UTR_variant	6/6	1	NM_004917.5	P1
KLK4	ENST00000597441.1	n.65G>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.846 AC: 94732 AN: 112004 Hom.: 41141 Cov.: 14

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.890

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.898

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.833

Gnomad MID AF: 0.945

Gnomad NFE AF: 0.851

Gnomad OTH AF: 0.868

GnomAD4 exome AF: 0.826 AC: 103270 AN: 125064 Hom.: 44669 Cov.: 0 AF XY: 0.820 AC XY: 54678 AN XY: 66662

Gnomad4 AFR exome AF: 0.934

Gnomad4 AMR exome AF: 0.839

Gnomad4 ASJ exome AF: 0.921

Gnomad4 EAS exome AF: 0.132

Gnomad4 SAS exome AF: 0.772

Gnomad4 FIN exome AF: 0.851

Gnomad4 NFE exome AF: 0.870

Gnomad4 OTH exome AF: 0.845

GnomAD4 genome AF: 0.846 AC: 94764 AN: 112046 Hom.: 41152 Cov.: 14 AF XY: 0.842 AC XY: 45349 AN XY: 53880

Gnomad4 AFR AF: 0.938

Gnomad4 AMR AF: 0.830

Gnomad4 ASJ AF: 0.898

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.719

Gnomad4 FIN AF: 0.833

Gnomad4 NFE AF: 0.851

Gnomad4 OTH AF: 0.859

Alfa AF: 0.864 Hom.: 5438

Bravo AF: 0.852

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.4
Dann	Benign	0.67

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: rs1654556; hg19: chr19-51409803;