7-142943481-C-T

Variant names:

• chr7-142943481-C-T
• rs573103646
• NM_000420.3:c.1703+5G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_000420.3(KEL):​c.1703+5G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000566 in 1,612,366 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00032 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00059 (13 hom.)
• Consequence: KEL NM_000420.3 splice_region, intron
• Scores: Splicing: ADA: 0.8791
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.195
• Publications: 0 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 7-142943481-C-T is Benign according to our data. Variant chr7-142943481-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3041437.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 13 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KEL	NM_000420.3	c.1703+5G>A		splice_region_variant, intron_variant	Intron 15 of 18	ENST00000355265.7	NP_000411.1
KEL	XM_005249993.2	c.1739+5G>A		splice_region_variant, intron_variant	Intron 15 of 18		XP_005250050.1
KEL	XM_047420357.1	c.1592+5G>A		splice_region_variant, intron_variant	Intron 14 of 17		XP_047276313.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KEL	ENST00000355265.7	c.1703+5G>A		splice_region_variant, intron_variant	Intron 15 of 18	1	NM_000420.3	ENSP00000347409.2
KEL	ENST00000470850.1	n.168+5G>A		splice_region_variant, intron_variant	Intron 2 of 3	2
KEL	ENST00000465697.1	n.*68G>A		downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.000322 AC: 49 AN: 152218 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00910

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00114 AC: 287 AN: 251162 AF XY: 0.00165

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000591 AC: 863 AN: 1460030 Hom.: 13 Cov.: 32 AF XY: 0.000895 AC XY: 650 AN XY: 726538

African (AFR) AF: 0.00 AC: 0 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39690

South Asian (SAS) AF: 0.00959 AC: 827 AN: 86208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5762

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110336

Other (OTH) AF: 0.000497 AC: 30 AN: 60324

GnomAD4 genome AF: 0.000322 AC: 49 AN: 152336 Hom.: 0 Cov.: 33 AF XY: 0.000497 AC XY: 37 AN XY: 74486

African (AFR) AF: 0.0000722 AC: 3 AN: 41566

American (AMR) AF: 0.00 AC: 0 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00911 AC: 44 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68024

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000152 Hom.: 0

Bravo AF: 0.000102

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

KEL-related disorder Benign:1

Feb 20, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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
BayesDel_noAF	Benign	-0.65
CADD	Benign	17
DANN	Benign	0.80
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.88
dbscSNV1_RF	Benign	0.55
SpliceAI score (max)		0.17		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: rs573103646; hg19: chr7-142640568;