rs2740502

Variant names:

• chr19-50822930-G-C
• rs2740502
• NM_002257.4:c.46+773C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-50822930-G-C
• chr19-50822930-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002257.4(KLK1):​c.46+773C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 983,158 control chromosomes in the GnomAD database, including 75,299 homozygotes. 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: 𝑓 0.34 (9076 hom., cov: 30)
  • Exomes 𝑓: 0.40 (66223 hom.)
• Consequence: KLK1 NM_002257.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.644
• Publications: 5 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51335 AN: 151820 Hom.: 9082 Cov.: 30

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.373

GnomAD2 exomes AF: 0.410 AC: 55 AN: 134 AF XY: 0.479

Gnomad AFR exome AF: 0.182

Gnomad AMR exome AF: 0.500

Gnomad ASJ exome AF: 0.333

Gnomad EAS exome AF: 0.200

Gnomad FIN exome AF: 0.500

Gnomad NFE exome AF: 0.500

Gnomad OTH exome AF: 0.375

GnomAD4 exome AF: 0.397 AC: 330157 AN: 831218 Hom.: 66223 Cov.: 27 AF XY: 0.398 AC XY: 152804 AN XY: 383938

African (AFR) AF: 0.230 AC: 3623 AN: 15762

American (AMR) AF: 0.307 AC: 301 AN: 980

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1900 AN: 5148

East Asian (EAS) AF: 0.204 AC: 739 AN: 3626

South Asian (SAS) AF: 0.335 AC: 5505 AN: 16418

European-Finnish (FIN) AF: 0.388 AC: 128 AN: 330

Middle Eastern (MID) AF: 0.425 AC: 688 AN: 1620

European-Non Finnish (NFE) AF: 0.404 AC: 307189 AN: 760072

Other (OTH) AF: 0.370 AC: 10084 AN: 27262

GnomAD4 genome AF: 0.338 AC: 51329 AN: 151940 Hom.: 9076 Cov.: 30 AF XY: 0.335 AC XY: 24851 AN XY: 74242

African (AFR) AF: 0.244 AC: 10095 AN: 41446

American (AMR) AF: 0.313 AC: 4784 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1279 AN: 3470

East Asian (EAS) AF: 0.210 AC: 1082 AN: 5148

South Asian (SAS) AF: 0.350 AC: 1682 AN: 4804

European-Finnish (FIN) AF: 0.372 AC: 3923 AN: 10552

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.400 AC: 27192 AN: 67928

Other (OTH) AF: 0.367 AC: 774 AN: 2110

Alfa AF: 0.261 Hom.: 774

Bravo AF: 0.330

Asia WGS AF: 0.250 AC: 872 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	14
DANN	Benign	0.67
PhyloP100		0.64
Mutation Taster		=299/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs2740502; hg19: chr19-51326186;