rs1701929

Positions:

• chr19-50908073-G-A
• chr19-50908073-G-C
• chr19-50908073-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000324041.6(KLK4):​c.612+286C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 501,390 control chromosomes in the GnomAD database, including 135,913 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (44967 hom., cov: 31)
  • Exomes 𝑓: 0.71 (90946 hom.)
• Consequence: KLK4 ENST00000324041.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.364

Genes affected

KLK4 (HGNC:6365): (kallikrein related peptidase 4) 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 a cluster on chromosome 19. In some tissues its expression is hormonally regulated. The expression pattern of a similar mouse protein in murine developing teeth supports a role for the protein in the degradation of enamel proteins. Several transcript variants encoding different proteins have been found for this gene. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 19-50908073-G-A is Benign according to our data. Variant chr19-50908073-G-A is described in ClinVar as [Benign]. Clinvar id is 1236060.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK4	NM_004917.5	c.612+286C>T		intron_variant		ENST00000324041.6	NP_004908.4
KLK4	NM_001302961.2	c.327+286C>T		intron_variant			NP_001289890.1
KLK4	NR_126566.2	n.601+286C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK4	ENST00000324041.6	c.612+286C>T		intron_variant		1	NM_004917.5	ENSP00000326159	P1

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115570 AN: 152052 Hom.: 44928 Cov.: 31

Gnomad AFR AF: 0.858

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.737

Gnomad ASJ AF: 0.816

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.758

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.793

GnomAD4 exome AF: 0.708 AC: 247145 AN: 349220 Hom.: 90946 Cov.: 3 AF XY: 0.701 AC XY: 128477 AN XY: 183396

Gnomad4 AFR exome AF: 0.859

Gnomad4 AMR exome AF: 0.710

Gnomad4 ASJ exome AF: 0.820

Gnomad4 EAS exome AF: 0.266

Gnomad4 SAS exome AF: 0.585

Gnomad4 FIN exome AF: 0.757

Gnomad4 NFE exome AF: 0.759

Gnomad4 OTH exome AF: 0.741

GnomAD4 genome AF: 0.760 AC: 115663 AN: 152170 Hom.: 44967 Cov.: 31 AF XY: 0.755 AC XY: 56137 AN XY: 74384

Gnomad4 AFR AF: 0.858

Gnomad4 AMR AF: 0.736

Gnomad4 ASJ AF: 0.816

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.566

Gnomad4 FIN AF: 0.758

Gnomad4 NFE AF: 0.754

Gnomad4 OTH AF: 0.785

Alfa AF: 0.765 Hom.: 42990

Bravo AF: 0.765

Asia WGS AF: 0.429 AC: 1497 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.6
DANN	Benign	0.53

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: rs1701929; hg19: chr19-51411329;