GeneBe

rs198966

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004917.5(KLK4):​c.300C>T​(p.Ser100Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00604 in 1,614,014 control chromosomes in the GnomAD database, including 503 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 250 hom., cov: 32)
Exomes 𝑓: 0.0034 ( 253 hom. )

Consequence

KLK4
NM_004917.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0190
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 19-50908754-G-A is Benign according to our data. Variant chr19-50908754-G-A is described in ClinVar as [Benign]. Clinvar id is 782657.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.019 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KLK4NM_004917.5 linkuse as main transcriptc.300C>T p.Ser100Ser synonymous_variant 4/6 ENST00000324041.6 NP_004908.4 Q9Y5K2A0A0C4DFQ5
KLK4NM_001302961.2 linkuse as main transcriptc.15C>T p.Ser5Ser synonymous_variant 3/5 NP_001289890.1 Q9Y5K2Q5BQA0
KLK4XM_011527545.4 linkuse as main transcriptc.300C>T p.Ser100Ser synonymous_variant 3/4 XP_011525847.1
KLK4NR_126566.2 linkuse as main transcriptn.293C>T non_coding_transcript_exon_variant 3/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KLK4ENST00000324041.6 linkuse as main transcriptc.300C>T p.Ser100Ser synonymous_variant 4/61 NM_004917.5 ENSP00000326159.1 A0A0C4DFQ5

Frequencies

GnomAD3 genomes
AF:
0.0310
AC:
4713
AN:
152056
Hom.:
250
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.108
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0106
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000622
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000456
Gnomad OTH
AF:
0.0177
GnomAD3 exomes
AF:
0.00804
AC:
2019
AN:
251164
Hom.:
97
AF XY:
0.00616
AC XY:
837
AN XY:
135826
show subpopulations
Gnomad AFR exome
AF:
0.107
Gnomad AMR exome
AF:
0.00529
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000229
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000572
Gnomad OTH exome
AF:
0.00473
GnomAD4 exome
AF:
0.00344
AC:
5022
AN:
1461840
Hom.:
253
Cov.:
32
AF XY:
0.00299
AC XY:
2177
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.118
Gnomad4 AMR exome
AF:
0.00613
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000197
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000298
Gnomad4 OTH exome
AF:
0.00715
GnomAD4 genome
AF:
0.0311
AC:
4731
AN:
152174
Hom.:
250
Cov.:
32
AF XY:
0.0297
AC XY:
2206
AN XY:
74376
show subpopulations
Gnomad4 AFR
AF:
0.108
Gnomad4 AMR
AF:
0.0105
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000622
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000456
Gnomad4 OTH
AF:
0.0176
Alfa
AF:
0.0161
Hom.:
71
Bravo
AF:
0.0362
Asia WGS
AF:
0.00895
AC:
31
AN:
3478
EpiCase
AF:
0.000436
EpiControl
AF:
0.000711

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 31, 2019- -
Benign, criteria provided, single submitterclinical testingGeneDxJun 09, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
1.3
DANN
Benign
0.54

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs198966; hg19: chr19-51412010; API