rs1722561

Positions:

• chr19-50996987-A-G

Variant summary

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

The NM_007196.4(KLK8):​c.627+764T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 150,666 control chromosomes in the GnomAD database, including 21,220 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 0.51 (21220 hom., cov: 28)
• Consequence: KLK8 NM_007196.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK8	NM_007196.4	c.627+764T>C		intron_variant		ENST00000695909.1	NP_009127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK8	ENST00000695909.1	c.627+764T>C		intron_variant			NM_007196.4	ENSP00000512260.1

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77127 AN: 150546 Hom.: 21199 Cov.: 28

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.515

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

GnomAD4 genome AF: 0.512 AC: 77192 AN: 150666 Hom.: 21220 Cov.: 28 AF XY: 0.505 AC XY: 37102 AN XY: 73506

Gnomad4 AFR AF: 0.712

Gnomad4 AMR AF: 0.526

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.249

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.510

Alfa AF: 0.255 Hom.: 485

Bravo AF: 0.533

Asia WGS AF: 0.265 AC: 923 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.0
DANN	Benign	0.30

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: rs1722561; hg19: chr19-51500243;