Variant rs61729032 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000420.3(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
NM_000420.3 missense

Scores

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]

KEL links:

KEL (HGNC:):

KEL links:

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
KEL	NM_000420.3 linkuse as main transcript	c.1481A>T	p.Glu494Val	missense_variant	13/19	ENST00000355265.7	NP_000411.1	P23276A0A077QP03
KEL	XM_005249993.2 linkuse as main transcript	c.1517A>T	p.Glu506Val	missense_variant	13/19		XP_005250050.1
KEL	XM_047420357.1 linkuse as main transcript	c.1370A>T	p.Glu457Val	missense_variant	12/18		XP_047276313.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KEL	ENST00000355265.7 linkuse as main transcript	c.1481A>T	p.Glu494Val	missense_variant	13/19	1	NM_000420.3	ENSP00000347409.2		P23276
KEL	ENST00000465697.1 linkuse as main transcript	n.342A>T		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes

AF:

0.00118

AC:

180

AN:

152132

Hom.:

Cov.:

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.:

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.:

Cov.:

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.:

Cov.:

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.:

Bravo

AF:

0.000419

ExAC

AF:

0.00175

AC:

212

Asia WGS

AF:

0.00231

AC:

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 provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 12, 2019

This 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

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.17

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.71

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.3

PrimateAI

Benign

0.27

PROVEAN

Benign

-2.3

REVEL

Uncertain

0.33

Sift

Benign

0.17

Sift4G

Uncertain

0.0060

Polyphen

0.79

Vest4

0.49

MVP

0.80

MPC

0.25

ClinPred

0.028

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over