19-51082358-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369775.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK14	NM_001369775.2	MANE Select	c.40+217G>A		intron	N/A	NP_001356704.1	A0A1R3UHJ7
	KLK14	NM_001311182.2		c.40+217G>A		intron	N/A	NP_001298111.2	A0A1R3UHJ7
	KLK14	NM_022046.6		c.40+217G>A		intron	N/A	NP_071329.3	A0A1R3UHJ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK14	ENST00000650543.2	MANE Select	c.40+217G>A		intron	N/A	ENSP00000497141.1	A0A1R3UHJ7
	KLK14	ENST00000156499.7	TSL:1	c.40+217G>A		intron	N/A	ENSP00000156499.3	A0A1R3UHJ7
	KLK14	ENST00000391802.1	TSL:5	c.88+217G>A		intron	N/A	ENSP00000375678.1	Q9P0G3

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

African (AFR) AF: 0.340 AC: 14059 AN: 41362

American (AMR) AF: 0.570 AC: 8703 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1554 AN: 3468

East Asian (EAS) AF: 0.609 AC: 3128 AN: 5134

South Asian (SAS) AF: 0.521 AC: 2509 AN: 4816

European-Finnish (FIN) AF: 0.501 AC: 5271 AN: 10522

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.476 AC: 32335 AN: 67914

Other (OTH) AF: 0.475 AC: 1002 AN: 2110

Alfa AF: 0.475 Hom.: 38037

Bravo AF: 0.454

Asia WGS AF: 0.562 AC: 1955 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.5
DANN	Benign	0.42
PhyloP100		-0.80
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2072689;

hg19: chr19-51585615;