19-51080471-C-G

Position:

• chr19-51080471-C-G

Variant summary

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

The NM_001369775.2(KLK14):​c.213-769G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 152,070 control chromosomes in the GnomAD database, including 13,162 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 0.39 (13162 hom., cov: 32)
• Consequence: KLK14 NM_001369775.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.985

Genes affected

KLK14 (HGNC:6362): (kallikrein related peptidase 14) This gene encodes a member of the kallikrein subfamily of serine proteases that have diverse physiological functions such as regulation of blood pressure and desquamation. The altered expression of this gene is implicated in the progression of different cancers including breast and prostate tumors. The encoded protein is a precursor that is proteolytically processed to generate the functional enzyme. This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK14	NM_001369775.2	c.213-769G>C		intron_variant		ENST00000650543.2	NP_001356704.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK14	ENST00000650543.2	c.213-769G>C		intron_variant			NM_001369775.2	ENSP00000497141.1
KLK14	ENST00000156499.7	c.213-769G>C		intron_variant		1		ENSP00000156499.3
KLK14	ENST00000391802.1	c.261-769G>C		intron_variant		5		ENSP00000375678.1

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59689 AN: 151952 Hom.: 13138 Cov.: 32

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.0863

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.393

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.393 AC: 59761 AN: 152070 Hom.: 13162 Cov.: 32 AF XY: 0.390 AC XY: 28976 AN XY: 74348

Gnomad4 AFR AF: 0.580

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.0859

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.388

Alfa AF: 0.178 Hom.: 304

Bravo AF: 0.397

Asia WGS AF: 0.273 AC: 951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.52
DANN	Benign	0.41

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: rs10445581; hg19: chr19-51583728;