Variant rs8176036 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_000420.3(KEL):c.1680A>C(p.Pro560Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0551 in 1,613,774 control chromosomes in the GnomAD database, including 3,365 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.088 ( 880 hom., cov: 33)

Exomes 𝑓: 0.052 ( 2485 hom. )

Consequence

KEL
NM_000420.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -3.17

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 made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 7-142943509-T-G is Benign according to our data. Variant chr7-142943509-T-G is described in ClinVar as [Benign]. Clinvar id is 3038127.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-3.17 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KEL	NM_000420.3 link	c.1680A>C	p.Pro560Pro	synonymous_variant	Exon 15 of 19	ENST00000355265.7	NP_000411.1	P23276A0A077QP03
KEL	XM_005249993.2 link	c.1716A>C	p.Pro572Pro	synonymous_variant	Exon 15 of 19		XP_005250050.1
KEL	XM_047420357.1 link	c.1569A>C	p.Pro523Pro	synonymous_variant	Exon 14 of 18		XP_047276313.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KEL	ENST00000355265.7 link	c.1680A>C	p.Pro560Pro	synonymous_variant	Exon 15 of 19	1	NM_000420.3	ENSP00000347409.2	P23276
KEL	ENST00000470850.1 link	n.145A>C		non_coding_transcript_exon_variant	Exon 2 of 4	2
KEL	ENST00000465697.1 link	n.*40A>C		downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0880

AC:

13387

AN:

152070

Hom.:

877

Cov.:

show subpopulations

Gnomad AFR

AF:

0.190

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0491

Gnomad ASJ

AF:

0.0320

Gnomad EAS

AF:

0.0264

Gnomad SAS

AF:

0.00580

Gnomad FIN

AF:

0.0694

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0524

Gnomad OTH

AF:

0.0809

GnomAD3 exomes

AF:

0.0505

AC:

12687

AN:

251368

Hom.:

529

AF XY:

0.0464

AC XY:

6301

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.193

Gnomad AMR exome

AF:

0.0279

Gnomad ASJ exome

AF:

0.0277

Gnomad EAS exome

AF:

0.0272

Gnomad SAS exome

AF:

0.00735

Gnomad FIN exome

AF:

0.0731

Gnomad NFE exome

AF:

0.0503

Gnomad OTH exome

AF:

0.0460

GnomAD4 exome

AF:

0.0517

AC:

75536

AN:

1461586

Hom.:

2485

Cov.:

AF XY:

0.0496

AC XY:

36093

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.188

Gnomad4 AMR exome

AF:

0.0279

Gnomad4 ASJ exome

AF:

0.0292

Gnomad4 EAS exome

AF:

0.0185

Gnomad4 SAS exome

AF:

0.00752

Gnomad4 FIN exome

AF:

0.0734

Gnomad4 NFE exome

AF:

0.0526

Gnomad4 OTH exome

AF:

0.0547

GnomAD4 genome

AF:

0.0881

AC:

13407

AN:

152188

Hom.:

880

Cov.:

AF XY:

0.0862

AC XY:

6412

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.190

Gnomad4 AMR

AF:

0.0490

Gnomad4 ASJ

AF:

0.0320

Gnomad4 EAS

AF:

0.0265

Gnomad4 SAS

AF:

0.00539

Gnomad4 FIN

AF:

0.0694

Gnomad4 NFE

AF:

0.0524

Gnomad4 OTH

AF:

0.0806

Alfa

AF:

0.0570

Hom.:

369

Bravo

AF:

0.0917

Asia WGS

AF:

0.0340

AC:

119

AN:

3478

EpiCase

AF:

0.0466

EpiControl

AF:

0.0500

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KEL-related disorder

Benign:1

Nov 25, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This 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

-0.76

CADD

Benign

0.033

DANN

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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.

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