rs9676881

chr19-10486104-G-Achr19-10486104-G-Cchr19-10486104-G-T

Variant summary

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

The 19-10486104-G-A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 208,742 control chromosomes in the GnomAD database, including 23,969 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 0.48 (18899 hom., cov: 32)
  • Exomes 𝑓: 0.41 (5070 hom.)
• Consequence: KEAP1 NM_203500.2 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.504

Genes affected

KEAP1 (HGNC:23177): (kelch like ECH associated protein 1) This gene encodes a protein containing KELCH-1 like domains, as well as a BTB/POZ domain. Kelch-like ECH-associated protein 1 interacts with NF-E2-related factor 2 in a redox-sensitive manner and the dissociation of the proteins in the cytoplasm is followed by transportation of NF-E2-related factor 2 to the nucleus. This interaction results in the expression of the catalytic subunit of gamma-glutamylcysteine synthetase. Two alternatively spliced transcript variants encoding the same isoform have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KEAP1	NM_203500.2			downstream_gene_variant		ENST00000171111.10
KEAP1	NM_012289.4			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KEAP1	ENST00000171111.10			downstream_gene_variant		1	NM_203500.2	P1
KEAP1	ENST00000393623.6			downstream_gene_variant		1		P1
KEAP1	ENST00000592478.5			downstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72107 AN: 151828 Hom.: 18856 Cov.: 32

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.551

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.465

GnomAD4 exome AF: 0.412 AC: 23372 AN: 56796 Hom.: 5070 Cov.: 0 AF XY: 0.408 AC XY: 10745 AN XY: 26312

Gnomad4 AFR exome AF: 0.704

Gnomad4 AMR exome AF: 0.322

Gnomad4 ASJ exome AF: 0.404

Gnomad4 EAS exome AF: 0.527

Gnomad4 SAS exome AF: 0.447

Gnomad4 FIN exome AF: 0.342

Gnomad4 NFE exome AF: 0.366

Gnomad4 OTH exome AF: 0.411

GnomAD4 genome AF: 0.475 AC: 72212 AN: 151946 Hom.: 18899 Cov.: 32 AF XY: 0.475 AC XY: 35247 AN XY: 74270

Gnomad4 AFR AF: 0.699

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.423

Gnomad4 EAS AF: 0.551

Gnomad4 SAS AF: 0.443

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.374

Gnomad4 OTH AF: 0.469

Alfa AF: 0.394 Hom.: 15351

Bravo AF: 0.482

Asia WGS AF: 0.508 AC: 1761 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.91
Dann	Benign	0.56

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9676881; hg19: chr19-10596780;