7-142943026-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000420.3(KEL):c.1790T>C(p.Leu597Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00498 in 1,614,116 control chromosomes in the GnomAD database, including 312 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 165 hom., cov: 33)

Exomes 𝑓: 0.0029 ( 147 hom. )

Consequence

KEL
NM_000420.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:2

Conservation

PhyloP100: 0.569

Publications

19 publications found

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]

KEL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025378764).

BP6

Variant 7-142943026-A-G is Benign according to our data. Variant chr7-142943026-A-G is described in ClinVar as [Benign]. Clinvar id is 31082.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KEL	NM_000420.3 link	c.1790T>C	p.Leu597Pro	missense_variant	Exon 17 of 19	ENST00000355265.7	NP_000411.1	P23276A0A077QP03
KEL	XM_005249993.2 link	c.1826T>C	p.Leu609Pro	missense_variant	Exon 17 of 19		XP_005250050.1
KEL	XM_047420357.1 link	c.1679T>C	p.Leu560Pro	missense_variant	Exon 16 of 18		XP_047276313.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KEL	ENST00000355265.7 link	c.1790T>C	p.Leu597Pro	missense_variant	Exon 17 of 19	1	NM_000420.3	ENSP00000347409.2	P23276
KEL	ENST00000478969.1 link	n.129T>C		non_coding_transcript_exon_variant	Exon 1 of 2	3
KEL	ENST00000470850.1 link	n.169-79T>C		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.0250

AC:

3811

AN:

152170

Hom.:

164

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0864

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00988

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.0197

GnomAD2 exomes

AF:

0.00674

AC:

1694

AN:

251394

AF XY:

0.00475

show subpopulations

Gnomad AFR exome

AF:

0.0890

Gnomad AMR exome

AF:

0.00437

Gnomad ASJ exome

AF:

0.00179

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000413

Gnomad OTH exome

AF:

0.00424

GnomAD4 exome

AF:

0.00288

AC:

4217

AN:

1461830

Hom.:

147

Cov.:

AF XY:

0.00255

AC XY:

1855

AN XY:

727218

show subpopulations

African (AFR)

AF:

0.0923

AC:

3090

AN:

33474

American (AMR)

AF:

0.00510

AC:

228

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00145

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000394

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00908

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

0.000352

AC:

391

AN:

1112010

Other (OTH)

AF:

0.00636

AC:

384

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

279

558

836

1115

1394

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0251

AC:

3816

AN:

152286

Hom.:

165

Cov.:

AF XY:

0.0242

AC XY:

1802

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0862

AC:

3583

AN:

41554

American (AMR)

AF:

0.00987

AC:

151

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00104

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000456

AC:

AN:

68020

Other (OTH)

AF:

0.0195

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

187

375

562

750

937

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0106

Hom.:

169

Bravo

AF:

0.0288

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0869

AC:

383

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00837

AC:

1016

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000711

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 04, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Kel6 antigen

Pathogenic:1

Oct 15, 2003

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.043

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.46

CADD

Benign

2.2

(source)

DANN

Benign

0.55

DEOGEN2

Benign

0.24

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.34

MetaRNN

Benign

0.0025

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.4

PhyloP100

0.57

PrimateAI

Benign

0.35

PROVEAN

Benign

4.7

REVEL

Benign

0.18

Sift

Benign

0.22

Sift4G

Benign

0.46

Polyphen

0.0

Vest4

0.11

MVP

0.50

MPC

0.093

ClinPred

0.00097

GERP RS

0.57

Varity_R

0.13

gMVP

0.40

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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7-142943026-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over