rs61729032

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

The ENST00000355265.7(KEL):​c.1481A>T​(p.Glu494Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000747 in 1,613,748 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00070 ( 7 hom. )

Consequence

KEL
ENST00000355265.7 missense

Scores

3
15

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.39
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 Likely_benign. Variant got -5 ACMG points.

BP6
Variant 7-142944333-T-A is Benign according to our data. Variant chr7-142944333-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 3035664.Status of the report is no_assertion_criteria_provided, 0 stars.
BS2
High Homozygotes in GnomAdExome4 at 7 BG gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KELNM_000420.3 linkuse as main transcriptc.1481A>T p.Glu494Val missense_variant 13/19 ENST00000355265.7 NP_000411.1
KELXM_005249993.2 linkuse as main transcriptc.1517A>T p.Glu506Val missense_variant 13/19 XP_005250050.1
KELXM_047420357.1 linkuse as main transcriptc.1370A>T p.Glu457Val missense_variant 12/18 XP_047276313.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KELENST00000355265.7 linkuse as main transcriptc.1481A>T p.Glu494Val missense_variant 13/191 NM_000420.3 ENSP00000347409 P1
KELENST00000465697.1 linkuse as main transcriptn.342A>T non_coding_transcript_exon_variant 2/43

Frequencies

GnomAD3 genomes
AF:
0.00118
AC:
180
AN:
152132
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00810
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.0113
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000235
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.00171
AC:
429
AN:
251478
Hom.:
0
AF XY:
0.00165
AC XY:
224
AN XY:
135914
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00712
Gnomad SAS exome
AF:
0.000261
Gnomad FIN exome
AF:
0.0112
Gnomad NFE exome
AF:
0.000360
Gnomad OTH exome
AF:
0.00114
GnomAD4 exome
AF:
0.000702
AC:
1026
AN:
1461498
Hom.:
7
Cov.:
30
AF XY:
0.000726
AC XY:
528
AN XY:
727078
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00501
Gnomad4 SAS exome
AF:
0.000417
Gnomad4 FIN exome
AF:
0.0125
Gnomad4 NFE exome
AF:
0.0000612
Gnomad4 OTH exome
AF:
0.000927
GnomAD4 genome
AF:
0.00118
AC:
180
AN:
152250
Hom.:
1
Cov.:
32
AF XY:
0.00154
AC XY:
115
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00812
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.0113
Gnomad4 NFE
AF:
0.000235
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000419
Hom.:
1
Bravo
AF:
0.000419
ExAC
AF:
0.00175
AC:
212
Asia WGS
AF:
0.00231
AC:
8
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

KEL-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesAug 12, 2019This variant is classified as likely 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
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.18
CADD
Benign
21
DANN
Benign
0.94
DEOGEN2
Benign
0.17
T
Eigen
Benign
-0.57
Eigen_PC
Benign
-0.67
FATHMM_MKL
Benign
0.24
N
LIST_S2
Benign
0.71
T
MetaRNN
Benign
0.011
T
MetaSVM
Benign
-0.83
T
MutationAssessor
Uncertain
2.3
M
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-2.3
N
REVEL
Uncertain
0.33
Sift
Benign
0.17
T
Sift4G
Uncertain
0.0060
D
Polyphen
0.79
P
Vest4
0.49
MVP
0.80
MPC
0.25
ClinPred
0.028
T
GERP RS
2.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.17
gMVP
0.65

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.32
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.32
Position offset: 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: rs61729032; hg19: chr7-142641420; API