Genetic Variant KLK1:c.46+773C>A (chr19-50822930-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002257.4(KLK1):c.46+773C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KLK1
NM_002257.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.644

Publications

5 publications found

Variant links:

Genes affected

KLK1 (HGNC:6357): (kallikrein 1) 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. This protein is functionally conserved in its capacity to release the vasoactive peptide, Lys-bradykinin, from low molecular weight kininogen. [provided by RefSeq, Jul 2008]

KLK1 Gene-Disease associations (from GenCC):

pulmonary arterial hypertension
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

KLK1 links:

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ACMG classification

Classification was made for transcript

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=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK1	NM_002257.4 link	c.46+773C>A		intron_variant	Intron 1 of 4	ENST00000301420.3	NP_002248.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
KLK1	ENST00000301420.3 link	c.46+773C>A	intron_variant	Intron 1 of 4	1	NM_002257.4	ENSP00000301420.1
KLK1	ENST00000593325.5 link	n.69C>A	non_coding_transcript_exon_variant	Exon 2 of 6	2		ENSP00000472939.1
KLK1	ENST00000593859.5 link	n.85+773C>A	intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

832896

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

384652

African (AFR)

AF:

0.00

AC:

AN:

15782

American (AMR)

AF:

0.00

AC:

AN:

984

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5158

East Asian (EAS)

AF:

0.00

AC:

AN:

3632

South Asian (SAS)

AF:

0.00

AC:

AN:

16450

European-Finnish (FIN)

AF:

0.00

AC:

AN:

330

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1620

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

761636

Other (OTH)

AF:

0.00

AC:

AN:

27304

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

774

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over