rs1701929

Variant names:

• chr19-50908073-G-A
• rs1701929
• ENST00000596876.1:n.900C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000596876.1(KLK4):​n.900C>T variant causes a non coding transcript exon 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 ENST00000596876.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.364
• Publications: 3 publications found

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]

KLK4 Gene-Disease associations (from GenCC):

• amelogenesis imperfecta type 2A1

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• amelogenesis imperfecta type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000596876.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK4	NM_004917.5	MANE Select	c.612+286C>T		intron	N/A	NP_004908.4
	KLK4	NM_001302961.2		c.327+286C>T		intron	N/A	NP_001289890.1
	KLK4	NR_126566.2		n.601+286C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK4	ENST00000596876.1	TSL:1	n.900C>T		non_coding_transcript_exon	Exon 2 of 2
	KLK4	ENST00000324041.6	TSL:1 MANE Select	c.612+286C>T		intron	N/A	ENSP00000326159.1
	KLK4	ENST00000431178.2	TSL:1	c.328+506C>T		intron	N/A	ENSP00000399448.2

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

African (AFR) AF: 0.859 AC: 8883 AN: 10342

American (AMR) AF: 0.710 AC: 10807 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.820 AC: 8908 AN: 10864

East Asian (EAS) AF: 0.266 AC: 6038 AN: 22704

South Asian (SAS) AF: 0.585 AC: 24865 AN: 42480

European-Finnish (FIN) AF: 0.757 AC: 14917 AN: 19700

Middle Eastern (MID) AF: 0.852 AC: 1319 AN: 1548

European-Non Finnish (NFE) AF: 0.759 AC: 156560 AN: 206322

Other (OTH) AF: 0.741 AC: 14848 AN: 20046

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

African (AFR) AF: 0.858 AC: 35620 AN: 41520

American (AMR) AF: 0.736 AC: 11259 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.816 AC: 2833 AN: 3472

East Asian (EAS) AF: 0.256 AC: 1324 AN: 5180

South Asian (SAS) AF: 0.566 AC: 2730 AN: 4822

European-Finnish (FIN) AF: 0.758 AC: 8010 AN: 10574

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.754 AC: 51289 AN: 67994

Other (OTH) AF: 0.785 AC: 1659 AN: 2114

Alfa AF: 0.765 Hom.: 63266

Bravo AF: 0.765

Asia WGS AF: 0.429 AC: 1497 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.6
DANN	Benign	0.53
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1701929; hg19: chr19-51411329;