rs1139132

Variant names:

• chr19-50906507-G-A
• rs1139132
• NM_004917.5:c.*427C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-50906507-G-A
• chr19-50906507-G-T

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.*427C>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 0.0000191 in 104,444 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: 22)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: KLK4 NM_004917.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380
• Publications: 1 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=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK4	NM_004917.5	c.*427C>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000324041.6	NP_004908.4
KLK4	NR_126566.2	n.1181C>T		non_coding_transcript_exon_variant	Exon 5 of 5
KLK4	NM_001302961.2	c.*427C>T		3_prime_UTR_variant	Exon 5 of 5		NP_001289890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK4	ENST00000324041.6	c.*427C>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_004917.5	ENSP00000326159.1
KLK4	ENST00000597441.1	n.105C>T		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.0000191 AC: 2 AN: 104444 Hom.: 0 Cov.: 0 AF XY: 0.0000181 AC XY: 1 AN XY: 55246

African (AFR) AF: 0.00 AC: 0 AN: 2042

American (AMR) AF: 0.00 AC: 0 AN: 5464

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2906

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 15358

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5210

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 338

European-Non Finnish (NFE) AF: 0.0000319 AC: 2 AN: 62612

Other (OTH) AF: 0.00 AC: 0 AN: 5342

GnomAD4 genome Cov.: 22

Alfa AF: 0.00 Hom.: 963

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
DANN	Benign	0.22
PhyloP100		0.038

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: rs1139132; hg19: chr19-51409763;