19-50908309-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004917.5(KLK4):c.612+50G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00532 in 1,605,664 control chromosomes in the GnomAD database, including 386 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.028 (195 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (191 hom.)
• Consequence: KLK4 NM_004917.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.119

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 19-50908309-C-T is Benign according to our data. Variant chr19-50908309-C-T is described in ClinVar as [Benign]. Clinvar id is 1245992.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLK4	NM_004917.5	c.612+50G>A		intron_variant		ENST00000324041.6
KLK4	NM_001302961.2	c.327+50G>A		intron_variant
KLK4	NR_126566.2	n.601+50G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLK4	ENST00000324041.6	c.612+50G>A		intron_variant		1	NM_004917.5	P1

Frequencies

GnomAD3 genomes AF: 0.0278 AC: 4224 AN: 152108 Hom.: 195 Cov.: 32

Gnomad AFR AF: 0.0970

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00923

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.0186

GnomAD3 exomes AF: 0.00731 AC: 1800 AN: 246274 Hom.: 80 AF XY: 0.00565 AC XY: 754 AN XY: 133458

Gnomad AFR exome AF: 0.0947

Gnomad AMR exome AF: 0.00512

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000486

Gnomad OTH exome AF: 0.00443

GnomAD4 exome AF: 0.00296 AC: 4300 AN: 1453438 Hom.: 191 Cov.: 32 AF XY: 0.00257 AC XY: 1860 AN XY: 723280

Gnomad4 AFR exome AF: 0.100

Gnomad4 AMR exome AF: 0.00552

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000163

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000273

Gnomad4 OTH exome AF: 0.00616

GnomAD4 genome AF: 0.0278 AC: 4237 AN: 152226 Hom.: 195 Cov.: 32 AF XY: 0.0270 AC XY: 2010 AN XY: 74434

Gnomad4 AFR AF: 0.0970

Gnomad4 AMR AF: 0.00921

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000441

Gnomad4 OTH AF: 0.0184

Alfa AF: 0.0116 Hom.: 21

Bravo AF: 0.0323

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	2.1
Dann	Benign	0.51

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: rs189903; hg19: chr19-51411565;