7-142948527-C-T

Position:

• chr7-142948527-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000420.3(KEL):​c.1204-2210G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0903 in 152,058 control chromosomes in the GnomAD database, including 1,001 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.090 (1001 hom., cov: 32)
• Consequence: KEL NM_000420.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.427

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KEL	NM_000420.3	c.1204-2210G>A		intron_variant		ENST00000355265.7
KEL	XM_005249993.2	c.1240-2210G>A		intron_variant
KEL	XM_047420357.1	c.1204-3786G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KEL	ENST00000355265.7	c.1204-2210G>A		intron_variant		1	NM_000420.3	P1
KEL	ENST00000479768.6	n.1322-1919G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0902 AC: 13699 AN: 151940 Hom.: 993 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0479

Gnomad ASJ AF: 0.0305

Gnomad EAS AF: 0.0266

Gnomad SAS AF: 0.00559

Gnomad FIN AF: 0.0689

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0487

Gnomad OTH AF: 0.0813

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0903 AC: 13737 AN: 152058 Hom.: 1001 Cov.: 32 AF XY: 0.0887 AC XY: 6592 AN XY: 74318

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.0478

Gnomad4 ASJ AF: 0.0305

Gnomad4 EAS AF: 0.0266

Gnomad4 SAS AF: 0.00518

Gnomad4 FIN AF: 0.0689

Gnomad4 NFE AF: 0.0487

Gnomad4 OTH AF: 0.0810

Alfa AF: 0.0756 Hom.: 116

Bravo AF: 0.0944

Asia WGS AF: 0.0370 AC: 127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.6
DANN	Benign	0.72

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

Other links and lift over

dbSNP: rs8176010; hg19: chr7-142645614;