rs1654553

Variant names:

• chr19-50907860-T-A
• rs1654553
• NM_004917.5:c.612+499A>T

Your query was ambiguous. Multiple possible variants found:

• chr19-50907860-T-A
• chr19-50907860-T-C
• chr19-50907860-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004917.5(KLK4):​c.612+499A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000012 in 83,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: KLK4 NM_004917.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.433
• Publications: 12 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK4	NM_004917.5	c.612+499A>T		intron_variant	Intron 5 of 5	ENST00000324041.6	NP_004908.4
KLK4	NM_001302961.2	c.327+499A>T		intron_variant	Intron 4 of 4		NP_001289890.1
KLK4	NR_126566.2	n.601+499A>T		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK4	ENST00000324041.6	c.612+499A>T		intron_variant	Intron 5 of 5	1	NM_004917.5	ENSP00000326159.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000120 AC: 1 AN: 83048 Hom.: 0 AF XY: 0.0000233 AC XY: 1 AN XY: 42944

African (AFR) AF: 0.00 AC: 0 AN: 2372

American (AMR) AF: 0.00 AC: 0 AN: 3900

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1958

East Asian (EAS) AF: 0.00 AC: 0 AN: 4332

South Asian (SAS) AF: 0.0000871 AC: 1 AN: 11484

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3748

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 50620

Other (OTH) AF: 0.00 AC: 0 AN: 4340

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.6
DANN	Benign	0.53
PhyloP100		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1654553; hg19: chr19-51411116;