Variant 7-142942917-T-C 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.1899A>G(p.Leu633Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 1,614,064 control chromosomes in the GnomAD database, including 1,890 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.062 ( 969 hom., cov: 33)

Exomes 𝑓: 0.0071 ( 921 hom. )

Consequence

KEL
NM_000420.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.380

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=-0.77).

BP6

Variant 7-142942917-T-C is Benign according to our data. Variant chr7-142942917-T-C is described in ClinVar as [Benign]. Clinvar id is 3056220.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.38 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KEL	NM_000420.3 link	c.1899A>G	p.Leu633Leu	synonymous_variant	Exon 17 of 19	ENST00000355265.7	NP_000411.1	P23276A0A077QP03
KEL	XM_005249993.2 link	c.1935A>G	p.Leu645Leu	synonymous_variant	Exon 17 of 19		XP_005250050.1
KEL	XM_047420357.1 link	c.1788A>G	p.Leu596Leu	synonymous_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.1899A>G	p.Leu633Leu	synonymous_variant	Exon 17 of 19	1	NM_000420.3	ENSP00000347409.2	P23276
KEL	ENST00000470850.1 link	n.199A>G		non_coding_transcript_exon_variant	Exon 3 of 4	2
KEL	ENST00000478969.1 link	n.238A>G		non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.0618

AC:

9400

AN:

152064

Hom.:

969

Cov.:

show subpopulations

Gnomad AFR

AF:

0.213

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0246

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00134

Gnomad OTH

AF:

0.0469

GnomAD3 exomes

AF:

0.0174

AC:

4362

AN:

251392

Hom.:

411

AF XY:

0.0122

AC XY:

1662

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.224

Gnomad AMR exome

AF:

0.0140

Gnomad ASJ exome

AF:

0.00198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00118

Gnomad OTH exome

AF:

0.0117

GnomAD4 exome

AF:

0.00714

AC:

10442

AN:

1461882

Hom.:

921

Cov.:

AF XY:

0.00621

AC XY:

4513

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.227

Gnomad4 AMR exome

AF:

0.0151

Gnomad4 ASJ exome

AF:

0.00145

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000580

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000947

Gnomad4 OTH exome

AF:

0.0149

GnomAD4 genome

AF:

0.0619

AC:

9414

AN:

152182

Hom.:

969

Cov.:

AF XY:

0.0582

AC XY:

4329

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.213

Gnomad4 AMR

AF:

0.0246

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00134

Gnomad4 OTH

AF:

0.0464

Alfa

AF:

0.0282

Hom.:

197

Bravo

AF:

0.0710

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.00131

EpiControl

AF:

0.00178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KEL-related disorder

Benign:1

Dec 18, 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

-0.77

CADD

Benign

4.0

DANN

Benign

0.50

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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