7-142943509-T-G

Variant names:

• chr7-142943509-T-G
• rs8176036
• NM_000420.3:c.1680A>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

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
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -3.17
• Publications: 8 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 -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	c.1680A>C	p.Pro560Pro	synonymous_variant	Exon 15 of 19	ENST00000355265.7	NP_000411.1
KEL	XM_005249993.2	c.1716A>C	p.Pro572Pro	synonymous_variant	Exon 15 of 19		XP_005250050.1
KEL	XM_047420357.1	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	Appris	UniProt
KEL	ENST00000355265.7	c.1680A>C	p.Pro560Pro	synonymous_variant	Exon 15 of 19	1	NM_000420.3	ENSP00000347409.2
KEL	ENST00000470850.1	n.145A>C		non_coding_transcript_exon_variant	Exon 2 of 4	2
KEL	ENST00000465697.1	n.*40A>C		downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.0880 AC: 13387 AN: 152070 Hom.: 877 Cov.: 33

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

GnomAD2 exomes AF: 0.0505 AC: 12687 AN: 251368 AF XY: 0.0464

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 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.: 33 AF XY: 0.0496 AC XY: 36093 AN XY: 727110

African (AFR) AF: 0.188 AC: 6301 AN: 33468

American (AMR) AF: 0.0279 AC: 1247 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0292 AC: 762 AN: 26136

East Asian (EAS) AF: 0.0185 AC: 736 AN: 39698

South Asian (SAS) AF: 0.00752 AC: 649 AN: 86254

European-Finnish (FIN) AF: 0.0734 AC: 3919 AN: 53418

Middle Eastern (MID) AF: 0.0258 AC: 149 AN: 5768

European-Non Finnish (NFE) AF: 0.0526 AC: 58470 AN: 1111740

Other (OTH) AF: 0.0547 AC: 3303 AN: 60380

GnomAD4 genome AF: 0.0881 AC: 13407 AN: 152188 Hom.: 880 Cov.: 33 AF XY: 0.0862 AC XY: 6412 AN XY: 74406

African (AFR) AF: 0.190 AC: 7901 AN: 41500

American (AMR) AF: 0.0490 AC: 749 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0320 AC: 111 AN: 3472

East Asian (EAS) AF: 0.0265 AC: 137 AN: 5168

South Asian (SAS) AF: 0.00539 AC: 26 AN: 4820

European-Finnish (FIN) AF: 0.0694 AC: 737 AN: 10626

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0524 AC: 3564 AN: 67988

Other (OTH) AF: 0.0806 AC: 170 AN: 2110

Alfa AF: 0.0698 Hom.: 961

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

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
PhyloP100		-3.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8176036; hg19: chr7-142640596;