Variant 19-10489863-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_203500.2(KEAP1):c.1326-10G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00363 in 1,610,238 control chromosomes in the GnomAD database, including 196 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.020 ( 108 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 88 hom. )

Consequence

KEAP1
NM_203500.2 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0006671

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.35

Variant links:

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]

KEAP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 19-10489863-C-T is Benign according to our data. Variant chr19-10489863-C-T is described in ClinVar as [Benign]. Clinvar id is 777416.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KEAP1	NM_203500.2 linkuse as main transcript	c.1326-10G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000171111.10
KEAP1	NM_012289.4 linkuse as main transcript	c.1326-10G>A		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
KEAP1	ENST00000171111.10 linkuse as main transcript	c.1326-10G>A	splice_polypyrimidine_tract_variant, intron_variant	1	NM_203500.2	P1
KEAP1	ENST00000393623.6 linkuse as main transcript	c.1326-10G>A	splice_polypyrimidine_tract_variant, intron_variant	1		P1
KEAP1	ENST00000592478.5 linkuse as main transcript	c.145-10G>A	splice_polypyrimidine_tract_variant, intron_variant	1
KEAP1	ENST00000590593.1 linkuse as main transcript	c.305-495G>A	intron_variant, NMD_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.0199

AC:

3030

AN:

152054

Hom.:

108

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0699

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00629

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.0125

GnomAD3 exomes

AF:

0.00496

AC:

1202

AN:

242322

Hom.:

AF XY:

0.00365

AC XY:

480

AN XY:

131370

show subpopulations

Gnomad AFR exome

AF:

0.0718

Gnomad AMR exome

AF:

0.00282

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000335

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000367

Gnomad OTH exome

AF:

0.00135

GnomAD4 exome

AF:

0.00193

AC:

2813

AN:

1458066

Hom.:

Cov.:

AF XY:

0.00156

AC XY:

1131

AN XY:

725040

show subpopulations

Gnomad4 AFR exome

AF:

0.0724

Gnomad4 AMR exome

AF:

0.00297

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000583

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000216

Gnomad4 OTH exome

AF:

0.00397

GnomAD4 genome

AF:

0.0199

AC:

3035

AN:

152172

Hom.:

108

Cov.:

AF XY:

0.0195

AC XY:

1452

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0698

Gnomad4 AMR

AF:

0.00629

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.0110

Hom.:

Bravo

AF:

0.0227

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00067

dbscSNV1_RF

Benign

0.034

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over