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GeneBe

7-142943509-T-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_000420.3(KEL):c.1680A>C(p.Pro560=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0551 in 1,613,774 control chromosomes in the GnomAD database, including 3,365 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.088 ( 880 hom., cov: 33)
Exomes 𝑓: 0.052 ( 2485 hom. )

Consequence

KEL
NM_000420.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.17
Variant links:
Genes affected
KEL (HGNC:6308): (Kell metallo-endopeptidase (Kell blood group)) This gene encodes a type II transmembrane glycoprotein that is the highly polymorphic Kell blood group antigen. The Kell glycoprotein links via a single disulfide bond to the XK membrane protein that carries the Kx antigen. The encoded protein contains sequence and structural similarity to members of the neprilysin (M13) family of zinc endopeptidases. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 7-142943509-T-G is Benign according to our data. Variant chr7-142943509-T-G is described in ClinVar as [Benign]. Clinvar id is 3038127.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.17 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
KELNM_000420.3 linkuse as main transcriptc.1680A>C p.Pro560= synonymous_variant 15/19 ENST00000355265.7
KELXM_005249993.2 linkuse as main transcriptc.1716A>C p.Pro572= synonymous_variant 15/19
KELXM_047420357.1 linkuse as main transcriptc.1569A>C p.Pro523= synonymous_variant 14/18

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KELENST00000355265.7 linkuse as main transcriptc.1680A>C p.Pro560= synonymous_variant 15/191 NM_000420.3 P1
KELENST00000470850.1 linkuse as main transcriptn.145A>C non_coding_transcript_exon_variant 2/42
KELENST00000465697.1 linkuse as main transcript downstream_gene_variant 3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0880
AC:
13387
AN:
152070
Hom.:
877
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.190
Gnomad AMI
AF:
0.00658
Gnomad AMR
AF:
0.0491
Gnomad ASJ
AF:
0.0320
Gnomad EAS
AF:
0.0264
Gnomad SAS
AF:
0.00580
Gnomad FIN
AF:
0.0694
Gnomad MID
AF:
0.0190
Gnomad NFE
AF:
0.0524
Gnomad OTH
AF:
0.0809
GnomAD3 exomes
AF:
0.0505
AC:
12687
AN:
251368
Hom.:
529
AF XY:
0.0464
AC XY:
6301
AN XY:
135830
show subpopulations
Gnomad AFR exome
AF:
0.193
Gnomad AMR exome
AF:
0.0279
Gnomad ASJ exome
AF:
0.0277
Gnomad EAS exome
AF:
0.0272
Gnomad SAS exome
AF:
0.00735
Gnomad FIN exome
AF:
0.0731
Gnomad NFE exome
AF:
0.0503
Gnomad OTH exome
AF:
0.0460
GnomAD4 exome
AF:
0.0517
AC:
75536
AN:
1461586
Hom.:
2485
Cov.:
33
AF XY:
0.0496
AC XY:
36093
AN XY:
727110
show subpopulations
Gnomad4 AFR exome
AF:
0.188
Gnomad4 AMR exome
AF:
0.0279
Gnomad4 ASJ exome
AF:
0.0292
Gnomad4 EAS exome
AF:
0.0185
Gnomad4 SAS exome
AF:
0.00752
Gnomad4 FIN exome
AF:
0.0734
Gnomad4 NFE exome
AF:
0.0526
Gnomad4 OTH exome
AF:
0.0547
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0881
AC:
13407
AN:
152188
Hom.:
880
Cov.:
33
AF XY:
0.0862
AC XY:
6412
AN XY:
74406
show subpopulations
Gnomad4 AFR
AF:
0.190
Gnomad4 AMR
AF:
0.0490
Gnomad4 ASJ
AF:
0.0320
Gnomad4 EAS
AF:
0.0265
Gnomad4 SAS
AF:
0.00539
Gnomad4 FIN
AF:
0.0694
Gnomad4 NFE
AF:
0.0524
Gnomad4 OTH
AF:
0.0806
Alfa
AF:
0.0570
Hom.:
369
Bravo
AF:
0.0917
Asia WGS
AF:
0.0340
AC:
119
AN:
3478
EpiCase
AF:
0.0466
EpiControl
AF:
0.0500

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

KEL-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesNov 25, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
Cadd
Benign
0.033
Dann
Benign
0.69

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs8176036; hg19: chr7-142640596; API