7-142954267-G-A

Variant names:

• chr7-142954267-G-A
• rs8176059
• NM_000420.3:c.841C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000420.3(KEL):​c.841C>T​(p.Arg281Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0093 in 1,614,062 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0068 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0096 (77 hom.)
• Consequence: KEL NM_000420.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0910
• Publications: 26 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.042672545).
• BS2: High Homozygotes in GnomAd4 at 5 BG gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000420.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KEL	NM_000420.3	MANE Select	c.841C>T	p.Arg281Trp	missense	Exon 8 of 19	NP_000411.1	A0A077QP03

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KEL	ENST00000355265.7	TSL:1 MANE Select	c.841C>T	p.Arg281Trp	missense	Exon 8 of 19	ENSP00000347409.2	P23276
	KEL	ENST00000949853.1		c.778C>T	p.Arg260Trp	missense	Exon 7 of 17	ENSP00000619912.1
	KEL	ENST00000479768.6	TSL:5	n.959C>T		non_coding_transcript_exon	Exon 8 of 11

Frequencies

GnomAD3 genomes AF: 0.00681 AC: 1036 AN: 152162 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00212

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00537

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00725

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0102

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.00698 AC: 1752 AN: 251154 AF XY: 0.00696

Gnomad AFR exome AF: 0.00215

Gnomad AMR exome AF: 0.00483

Gnomad ASJ exome AF: 0.0210

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00676

Gnomad NFE exome AF: 0.00968

Gnomad OTH exome AF: 0.00686

GnomAD4 exome AF: 0.00956 AC: 13977 AN: 1461782 Hom.: 77 Cov.: 33 AF XY: 0.00933 AC XY: 6784 AN XY: 727192

African (AFR) AF: 0.00152 AC: 51 AN: 33480

American (AMR) AF: 0.00503 AC: 225 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0231 AC: 605 AN: 26136

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39700

South Asian (SAS) AF: 0.00220 AC: 190 AN: 86258

European-Finnish (FIN) AF: 0.00594 AC: 317 AN: 53352

Middle Eastern (MID) AF: 0.00347 AC: 20 AN: 5768

European-Non Finnish (NFE) AF: 0.0108 AC: 11977 AN: 1111970

Other (OTH) AF: 0.00970 AC: 586 AN: 60394

GnomAD4 genome AF: 0.00681 AC: 1037 AN: 152280 Hom.: 5 Cov.: 32 AF XY: 0.00616 AC XY: 459 AN XY: 74480

African (AFR) AF: 0.00212 AC: 88 AN: 41552

American (AMR) AF: 0.00536 AC: 82 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0164 AC: 57 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00290 AC: 14 AN: 4822

European-Finnish (FIN) AF: 0.00725 AC: 77 AN: 10624

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0102 AC: 693 AN: 68016

Other (OTH) AF: 0.0114 AC: 24 AN: 2110

Alfa AF: 0.00894 Hom.: 16

Bravo AF: 0.00655

TwinsUK AF: 0.0102 AC: 38

ALSPAC AF: 0.0101 AC: 39

ESP6500AA AF: 0.00272 AC: 12

ESP6500EA AF: 0.0103 AC: 89

ExAC AF: 0.00717 AC: 871

Asia WGS AF: 0.00144 AC: 6 AN: 3478

EpiCase AF: 0.0100

EpiControl AF: 0.00937

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.64	D
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	1.9	M
PhyloP100		0.091
PrimateAI	Benign	0.18	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.22
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.017	D
Polyphen		1.0	D
Vest4		0.34
MVP		0.78
MPC		0.32
ClinPred		0.074	T
GERP RS		-1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.43
gMVP		0.42
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs8176059; hg19: chr7-142651354;