19-50906507-G-T

Position:

• chr19-50906507-G-T

Variant summary

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

The NM_004917.5(KLK4):​c.*427C>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 0.258 in 237,216 control chromosomes in the GnomAD database, including 11,440 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 0.36 (9962 hom., cov: 22)
  • Exomes 𝑓: 0.12 (1478 hom.)
• Consequence: KLK4 NM_004917.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK4	NM_004917.5	c.*427C>A		3_prime_UTR_variant	6/6	ENST00000324041.6	NP_004908.4
KLK4	NM_001302961.2	c.*427C>A		3_prime_UTR_variant	5/5		NP_001289890.1
KLK4	NR_126566.2	n.1181C>A		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK4	ENST00000324041.6	c.*427C>A		3_prime_UTR_variant	6/6	1	NM_004917.5	ENSP00000326159	P1
KLK4	ENST00000597441.1	n.105C>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.364 AC: 49250 AN: 135418 Hom.: 9950 Cov.: 22

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.371

GnomAD4 exome AF: 0.118 AC: 12016 AN: 101730 Hom.: 1478 Cov.: 0 AF XY: 0.115 AC XY: 6180 AN XY: 53820

Gnomad4 AFR exome AF: 0.176

Gnomad4 AMR exome AF: 0.141

Gnomad4 ASJ exome AF: 0.0777

Gnomad4 EAS exome AF: 0.0510

Gnomad4 SAS exome AF: 0.129

Gnomad4 FIN exome AF: 0.104

Gnomad4 NFE exome AF: 0.120

Gnomad4 OTH exome AF: 0.119

GnomAD4 genome AF: 0.364 AC: 49274 AN: 135486 Hom.: 9962 Cov.: 22 AF XY: 0.359 AC XY: 23634 AN XY: 65882

Gnomad4 AFR AF: 0.453

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.367

Alfa AF: 0.341 Hom.: 963

Asia WGS AF: 0.177 AC: 551 AN: 3100

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.29

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: rs1139132; hg19: chr19-51409763;