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GeneBe

7-142943829-G-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_000420.3(KEL):c.1546C>A(p.Arg516=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00353 in 1,614,170 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.010 ( 12 hom., cov: 32)
Exomes 𝑓: 0.0028 ( 35 hom. )

Consequence

KEL
NM_000420.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.21
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=-0.75).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 7-142943829-G-T is Benign according to our data. Variant chr7-142943829-G-T is described in ClinVar as [Benign]. Clinvar id is 784500.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=3.2 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0101 (1538/152286) while in subpopulation AFR AF= 0.0282 (1171/41556). AF 95% confidence interval is 0.0268. There are 12 homozygotes in gnomad4. There are 758 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 12 BG gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
KELNM_000420.3 linkuse as main transcriptc.1546C>A p.Arg516= synonymous_variant 14/19 ENST00000355265.7
KELXM_005249993.2 linkuse as main transcriptc.1582C>A p.Arg528= synonymous_variant 14/19
KELXM_047420357.1 linkuse as main transcriptc.1435C>A p.Arg479= synonymous_variant 13/18

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KELENST00000355265.7 linkuse as main transcriptc.1546C>A p.Arg516= synonymous_variant 14/191 NM_000420.3 P1
KELENST00000465697.1 linkuse as main transcriptn.407C>A non_coding_transcript_exon_variant 3/43
KELENST00000470850.1 linkuse as main transcriptn.11C>A non_coding_transcript_exon_variant 1/42

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0101
AC:
1534
AN:
152168
Hom.:
12
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0281
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00916
Gnomad ASJ
AF:
0.0251
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0253
Gnomad NFE
AF:
0.00156
Gnomad OTH
AF:
0.0129
GnomAD3 exomes
AF:
0.00480
AC:
1206
AN:
251300
Hom.:
4
AF XY:
0.00434
AC XY:
589
AN XY:
135832
show subpopulations
Gnomad AFR exome
AF:
0.0299
Gnomad AMR exome
AF:
0.00552
Gnomad ASJ exome
AF:
0.0258
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000359
Gnomad FIN exome
AF:
0.0000925
Gnomad NFE exome
AF:
0.00194
Gnomad OTH exome
AF:
0.00587
GnomAD4 exome
AF:
0.00285
AC:
4163
AN:
1461884
Hom.:
35
Cov.:
33
AF XY:
0.00281
AC XY:
2043
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.0298
Gnomad4 AMR exome
AF:
0.00608
Gnomad4 ASJ exome
AF:
0.0264
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000301
Gnomad4 FIN exome
AF:
0.0000936
Gnomad4 NFE exome
AF:
0.00153
Gnomad4 OTH exome
AF:
0.00672
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0101
AC:
1538
AN:
152286
Hom.:
12
Cov.:
32
AF XY:
0.0102
AC XY:
758
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.0282
Gnomad4 AMR
AF:
0.00915
Gnomad4 ASJ
AF:
0.0251
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00154
Gnomad4 OTH
AF:
0.0128
Alfa
AF:
0.00670
Hom.:
4
Bravo
AF:
0.0114
Asia WGS
AF:
0.00289
AC:
10
AN:
3478

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMay 21, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.75
Cadd
Benign
8.9
Dann
Benign
0.82
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs8176034; hg19: chr7-142640916; API