19-51082358-C-T

Variant names:

• chr19-51082358-C-T
• rs2072689
• NM_001369775.2:c.40+217G>A

Variant summary

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

The NM_001369775.2(KLK14):​c.40+217G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 151,786 control chromosomes in the GnomAD database, including 16,280 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 0.46 (16280 hom., cov: 30)
• Consequence: KLK14 NM_001369775.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.802

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK14	NM_001369775.2	c.40+217G>A		intron_variant	Intron 2 of 5	ENST00000650543.2	NP_001356704.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK14	ENST00000650543.2	c.40+217G>A		intron_variant	Intron 2 of 5		NM_001369775.2	ENSP00000497141.1
KLK14	ENST00000156499.7	c.40+217G>A		intron_variant	Intron 3 of 7	1		ENSP00000156499.3
KLK14	ENST00000391802.1	c.88+217G>A		intron_variant	Intron 3 of 6	5		ENSP00000375678.1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69162 AN: 151668 Hom.: 16252 Cov.: 30

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.471

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

GnomAD4 genome AF: 0.456 AC: 69248 AN: 151786 Hom.: 16280 Cov.: 30 AF XY: 0.463 AC XY: 34325 AN XY: 74144

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.609

Gnomad4 SAS AF: 0.521

Gnomad4 FIN AF: 0.501

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.475

Alfa AF: 0.478 Hom.: 26046

Bravo AF: 0.454

Asia WGS AF: 0.562 AC: 1955 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.5
DANN	Benign	0.42

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: rs2072689; hg19: chr19-51585615;