Variant rs11545829 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_203500.2(KEAP1):c.1611C>T(p.Tyr537Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0161 in 1,613,870 control chromosomes in the GnomAD database, including 2,481 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 0.020 ( 266 hom., cov: 31)

Exomes 𝑓: 0.016 ( 2215 hom. )

Consequence

KEAP1
NM_203500.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.263

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:

KEAP1 (HGNC:):

KEAP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP7

Synonymous conserved (PhyloP=-0.263 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KEAP1	NM_203500.2 linkuse as main transcript	c.1611C>T	p.Tyr537Tyr	synonymous_variant	5/6	ENST00000171111.10	NP_987096.1	Q14145A0A024R7C0
KEAP1	NM_012289.4 linkuse as main transcript	c.1611C>T	p.Tyr537Tyr	synonymous_variant	5/6		NP_036421.2	Q14145A0A024R7C0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KEAP1	ENST00000171111.10 linkuse as main transcript	c.1611C>T	p.Tyr537Tyr	synonymous_variant	5/6	1	NM_203500.2	ENSP00000171111.4		Q14145

Frequencies

GnomAD3 genomes

AF:

0.0204

AC:

3096

AN:

151938

Hom.:

265

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00792

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0508

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.295

Gnomad SAS

AF:

0.0672

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00110

Gnomad OTH

AF:

0.0207

GnomAD3 exomes

AF:

0.0416

AC:

10465

AN:

251306

Hom.:

951

AF XY:

0.0390

AC XY:

5297

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.00868

Gnomad AMR exome

AF:

0.0839

Gnomad ASJ exome

AF:

0.00655

Gnomad EAS exome

AF:

0.289

Gnomad SAS exome

AF:

0.0543

Gnomad FIN exome

AF:

0.00300

Gnomad NFE exome

AF:

0.00149

Gnomad OTH exome

AF:

0.0245

GnomAD4 exome

AF:

0.0156

AC:

22857

AN:

1461814

Hom.:

2215

Cov.:

AF XY:

0.0163

AC XY:

11861

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.00798

Gnomad4 AMR exome

AF:

0.0818

Gnomad4 ASJ exome

AF:

0.00585

Gnomad4 EAS exome

AF:

0.293

Gnomad4 SAS exome

AF:

0.0537

Gnomad4 FIN exome

AF:

0.00270

Gnomad4 NFE exome

AF:

0.000701

Gnomad4 OTH exome

AF:

0.0261

GnomAD4 genome

AF:

0.0204

AC:

3109

AN:

152056

Hom.:

266

Cov.:

AF XY:

0.0229

AC XY:

1702

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.00800

Gnomad4 AMR

AF:

0.0512

Gnomad4 ASJ

AF:

0.00548

Gnomad4 EAS

AF:

0.296

Gnomad4 SAS

AF:

0.0671

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.00110

Gnomad4 OTH

AF:

0.0209

Alfa

AF:

0.00890

Hom.:

169

Bravo

AF:

0.0261

Asia WGS

AF:

0.166

AC:

574

AN:

3478

EpiCase

AF:

0.000927

EpiControl

AF:

0.00113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.12

DANN

Benign

0.35

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over