chr19-51000268-T-C

Position:

• chr19-51000268-T-C

Variant summary

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

The NM_007196.4(KLK8):​c.231-10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 1,566,868 control chromosomes in the GnomAD database, including 169,797 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 0.55 (25461 hom., cov: 29)
  • Exomes 𝑓: 0.44 (144336 hom.)
• Consequence: KLK8 NM_007196.4 intron
• Scores: Splicing: ADA: 0.00002932
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

Genes affected

KLK8 (HGNC:6369): (kallikrein related peptidase 8) 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 tandem in a gene cluster on chromosome 19. The encoded protein may be involved in proteolytic cascade in the skin and may serve as a biomarker for ovarian cancer. Alternate splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

ENSG00000267879 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK8	NM_007196.4	c.231-10A>G		intron_variant		ENST00000695909.1	NP_009127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK8	ENST00000695909.1	c.231-10A>G		intron_variant			NM_007196.4	ENSP00000512260.1

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83458 AN: 151556 Hom.: 25417 Cov.: 29

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.483

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.547

GnomAD3 exomes AF: 0.472 AC: 106393 AN: 225524 Hom.: 26748 AF XY: 0.455 AC XY: 54551 AN XY: 119982

Gnomad AFR exome AF: 0.832

Gnomad AMR exome AF: 0.570

Gnomad ASJ exome AF: 0.470

Gnomad EAS exome AF: 0.420

Gnomad SAS exome AF: 0.325

Gnomad FIN exome AF: 0.390

Gnomad NFE exome AF: 0.442

Gnomad OTH exome AF: 0.463

GnomAD4 exome AF: 0.445 AC: 629404 AN: 1415196 Hom.: 144336 Cov.: 43 AF XY: 0.439 AC XY: 305486 AN XY: 696094

Gnomad4 AFR exome AF: 0.845

Gnomad4 AMR exome AF: 0.566

Gnomad4 ASJ exome AF: 0.469

Gnomad4 EAS exome AF: 0.371

Gnomad4 SAS exome AF: 0.324

Gnomad4 FIN exome AF: 0.397

Gnomad4 NFE exome AF: 0.440

Gnomad4 OTH exome AF: 0.470

GnomAD4 genome AF: 0.551 AC: 83559 AN: 151672 Hom.: 25461 Cov.: 29 AF XY: 0.542 AC XY: 40184 AN XY: 74094

Gnomad4 AFR AF: 0.827

Gnomad4 AMR AF: 0.560

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.440

Gnomad4 OTH AF: 0.544

Alfa AF: 0.513 Hom.: 4342

Bravo AF: 0.579

Asia WGS AF: 0.359 AC: 1249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.75
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000029
dbscSNV1_RF	Benign	0.0040
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: rs1701946; hg19: chr19-51503524; COSMIC: COSV51593960; COSMIC: COSV51593960;