rs73042387

Positions:

• chr19-50906915-G-A

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.*19C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,613,344 control chromosomes in the GnomAD database, including 14,700 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1148 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13552 hom.)
• Consequence: KLK4 ENST00000324041.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.110

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=-0.87).
• BP6: Variant 19-50906915-G-A is Benign according to our data. Variant chr19-50906915-G-A is described in ClinVar as [Benign]. Clinvar id is 259563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50906915-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK4	NM_004917.5	c.*19C>T		3_prime_UTR_variant	6/6	ENST00000324041.6	NP_004908.4
KLK4	NM_001302961.2	c.*19C>T		3_prime_UTR_variant	5/5		NP_001289890.1
KLK4	NR_126566.2	n.773C>T		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK4	ENST00000324041.6	c.*19C>T		3_prime_UTR_variant	6/6	1	NM_004917.5	ENSP00000326159	P1

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17450 AN: 152038 Hom.: 1152 Cov.: 32

Gnomad AFR AF: 0.0976

Gnomad AMI AF: 0.0956

Gnomad AMR AF: 0.0856

Gnomad ASJ AF: 0.0960

Gnomad EAS AF: 0.00924

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.122

GnomAD3 exomes AF: 0.117 AC: 29414 AN: 251472 Hom.: 2029 AF XY: 0.123 AC XY: 16716 AN XY: 135914

Gnomad AFR exome AF: 0.0965

Gnomad AMR exome AF: 0.0681

Gnomad ASJ exome AF: 0.0814

Gnomad EAS exome AF: 0.00821

Gnomad SAS exome AF: 0.175

Gnomad FIN exome AF: 0.105

Gnomad NFE exome AF: 0.142

Gnomad OTH exome AF: 0.124

GnomAD4 exome AF: 0.132 AC: 192860 AN: 1461190 Hom.: 13552 Cov.: 32 AF XY: 0.134 AC XY: 97175 AN XY: 726980

Gnomad4 AFR exome AF: 0.0999

Gnomad4 AMR exome AF: 0.0713

Gnomad4 ASJ exome AF: 0.0848

Gnomad4 EAS exome AF: 0.00564

Gnomad4 SAS exome AF: 0.174

Gnomad4 FIN exome AF: 0.107

Gnomad4 NFE exome AF: 0.139

Gnomad4 OTH exome AF: 0.126

GnomAD4 genome AF: 0.115 AC: 17444 AN: 152154 Hom.: 1148 Cov.: 32 AF XY: 0.113 AC XY: 8374 AN XY: 74406

Gnomad4 AFR AF: 0.0975

Gnomad4 AMR AF: 0.0855

Gnomad4 ASJ AF: 0.0960

Gnomad4 EAS AF: 0.00907

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.121

Alfa AF: 0.123 Hom.: 337

Bravo AF: 0.111

Asia WGS AF: 0.0680 AC: 237 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.47

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: rs73042387; hg19: chr19-51410171;