Variant 19-10499560-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_203500.2(KEAP1):c.474T>C(p.Gly158=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.092 in 1,614,064 control chromosomes in the GnomAD database, including 7,612 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

Frequency

Genomes: 𝑓 0.11 ( 1092 hom., cov: 32)

Exomes 𝑓: 0.090 ( 6520 hom. )

Consequence

KEAP1
NM_203500.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.24

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 19-10499560-A-G is Benign according to our data. Variant chr19-10499560-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-5.24 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.173 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.474T>C	p.Gly158=	synonymous_variant	2/6	ENST00000171111.10	NP_987096.1
KEAP1	NM_012289.4 linkuse as main transcript	c.474T>C	p.Gly158=	synonymous_variant	2/6		NP_036421.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KEAP1	ENST00000171111.10 linkuse as main transcript	c.474T>C	p.Gly158=	synonymous_variant	2/6	1	NM_203500.2	ENSP00000171111	P1

Frequencies

GnomAD3 genomes

AF:

0.110

AC:

16698

AN:

152172

Hom.:

1086

Cov.:

show subpopulations

Gnomad AFR

AF:

0.176

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.0765

Gnomad ASJ

AF:

0.0738

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0252

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0907

Gnomad OTH

AF:

0.111

GnomAD3 exomes

AF:

0.0798

AC:

19986

AN:

250442

Hom.:

1036

AF XY:

0.0770

AC XY:

10436

AN XY:

135450

show subpopulations

Gnomad AFR exome

AF:

0.178

Gnomad AMR exome

AF:

0.0481

Gnomad ASJ exome

AF:

0.0750

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0240

Gnomad FIN exome

AF:

0.129

Gnomad NFE exome

AF:

0.0945

Gnomad OTH exome

AF:

0.0802

GnomAD4 exome

AF:

0.0902

AC:

131823

AN:

1461774

Hom.:

6520

Cov.:

AF XY:

0.0878

AC XY:

63869

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.183

Gnomad4 AMR exome

AF:

0.0515

Gnomad4 ASJ exome

AF:

0.0776

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0263

Gnomad4 FIN exome

AF:

0.127

Gnomad4 NFE exome

AF:

0.0957

Gnomad4 OTH exome

AF:

0.0882

GnomAD4 genome

AF:

0.110

AC:

16726

AN:

152290

Hom.:

1092

Cov.:

AF XY:

0.108

AC XY:

8077

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.176

Gnomad4 AMR

AF:

0.0763

Gnomad4 ASJ

AF:

0.0738

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0252

Gnomad4 FIN

AF:

0.126

Gnomad4 NFE

AF:

0.0907

Gnomad4 OTH

AF:

0.110

Alfa

AF:

0.0960

Hom.:

1001

Bravo

AF:

0.112

Asia WGS

AF:

0.0320

AC:

111

AN:

3478

EpiCase

AF:

0.0918

EpiControl

AF:

0.0958

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.20

DANN

Benign

0.52

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