19-51080679-G-T

Variant names:

• chr19-51080679-G-T
• rs9304708
• NM_001369775.2:c.212+853C>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.212+853C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 151,932 control chromosomes in the GnomAD database, including 13,091 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 (13091 hom., cov: 31)
• Consequence: KLK14 NM_001369775.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92
• Publications: 2 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.575 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK14	NM_001369775.2	MANE Select	c.212+853C>A		intron	N/A	NP_001356704.1
	KLK14	NM_001311182.2		c.212+853C>A		intron	N/A	NP_001298111.2
	KLK14	NM_022046.6		c.212+853C>A		intron	N/A	NP_071329.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK14	ENST00000650543.2	MANE Select	c.212+853C>A		intron	N/A	ENSP00000497141.1
	KLK14	ENST00000156499.7	TSL:1	c.212+853C>A		intron	N/A	ENSP00000156499.3
	KLK14	ENST00000391802.1	TSL:5	c.260+853C>A		intron	N/A	ENSP00000375678.1

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59445 AN: 151814 Hom.: 13068 Cov.: 31

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.0867

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.392 AC: 59513 AN: 151932 Hom.: 13091 Cov.: 31 AF XY: 0.389 AC XY: 28849 AN XY: 74242

African (AFR) AF: 0.581 AC: 24050 AN: 41416

American (AMR) AF: 0.298 AC: 4550 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1390 AN: 3470

East Asian (EAS) AF: 0.0863 AC: 445 AN: 5154

South Asian (SAS) AF: 0.441 AC: 2118 AN: 4802

European-Finnish (FIN) AF: 0.293 AC: 3092 AN: 10568

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22456 AN: 67938

Other (OTH) AF: 0.387 AC: 814 AN: 2106

Alfa AF: 0.338 Hom.: 11647

Bravo AF: 0.395

Asia WGS AF: 0.273 AC: 951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.21
DANN	Benign	0.37
PhyloP100		-1.9
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

Other links and lift over

dbSNP: rs9304708; hg19: chr19-51583936;