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GeneBe

7-142942917-T-C

Variant summary

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

The NM_000420.3(KEL):c.1899A>G(p.Leu633=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 1,614,064 control chromosomes in the GnomAD database, including 1,890 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.062 ( 969 hom., cov: 33)
Exomes 𝑓: 0.0071 ( 921 hom. )

Consequence

KEL
NM_000420.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.380
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]

Genome browser will be placed here

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=-0.77).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 7-142942917-T-C is Benign according to our data. Variant chr7-142942917-T-C is described in ClinVar as [Benign]. Clinvar id is 3056220.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=0.38 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 = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
KELNM_000420.3 linkuse as main transcriptc.1899A>G p.Leu633= synonymous_variant 17/19 ENST00000355265.7
KELXM_005249993.2 linkuse as main transcriptc.1935A>G p.Leu645= synonymous_variant 17/19
KELXM_047420357.1 linkuse as main transcriptc.1788A>G p.Leu596= synonymous_variant 16/18

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KELENST00000355265.7 linkuse as main transcriptc.1899A>G p.Leu633= synonymous_variant 17/191 NM_000420.3 P1
KELENST00000470850.1 linkuse as main transcriptn.199A>G non_coding_transcript_exon_variant 3/42
KELENST00000478969.1 linkuse as main transcriptn.238A>G non_coding_transcript_exon_variant 1/23

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0618
AC:
9400
AN:
152064
Hom.:
969
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.213
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0246
Gnomad ASJ
AF:
0.00144
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00166
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.00134
Gnomad OTH
AF:
0.0469
GnomAD3 exomes
AF:
0.0174
AC:
4362
AN:
251392
Hom.:
411
AF XY:
0.0122
AC XY:
1662
AN XY:
135880
show subpopulations
Gnomad AFR exome
AF:
0.224
Gnomad AMR exome
AF:
0.0140
Gnomad ASJ exome
AF:
0.00198
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00118
Gnomad OTH exome
AF:
0.0117
GnomAD4 exome
AF:
0.00714
AC:
10442
AN:
1461882
Hom.:
921
Cov.:
33
AF XY:
0.00621
AC XY:
4513
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.227
Gnomad4 AMR exome
AF:
0.0151
Gnomad4 ASJ exome
AF:
0.00145
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000580
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000947
Gnomad4 OTH exome
AF:
0.0149
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0619
AC:
9414
AN:
152182
Hom.:
969
Cov.:
33
AF XY:
0.0582
AC XY:
4329
AN XY:
74396
show subpopulations
Gnomad4 AFR
AF:
0.213
Gnomad4 AMR
AF:
0.0246
Gnomad4 ASJ
AF:
0.00144
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00166
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00134
Gnomad4 OTH
AF:
0.0464
Alfa
AF:
0.0282
Hom.:
197
Bravo
AF:
0.0710
Asia WGS
AF:
0.0120
AC:
41
AN:
3478
EpiCase
AF:
0.00131
EpiControl
AF:
0.00178

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 SciencesDec 18, 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
-0.77
Cadd
Benign
4.0
Dann
Benign
0.50
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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: rs8176039; hg19: chr7-142640004; COSMIC: COSV62336775; COSMIC: COSV62336775; API