Variant 19-10486666-TCTG-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PM4_SupportingBP6_ModerateBS2

The NM_203500.2(KEAP1):c.1858_1860delCAG(p.Gln620del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.00332 in 1,614,072 control chromosomes in the GnomAD database, including 13 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0035 ( 13 hom. )

Consequence

KEAP1
NM_203500.2 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.04

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 Likely_benign. Variant got -5 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_203500.2. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 19-10486666-TCTG-T is Benign according to our data. Variant chr19-10486666-TCTG-T is described in ClinVar as [Likely_benign]. Clinvar id is 773348.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 300 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KEAP1	NM_203500.2 linkuse as main transcript	c.1858_1860delCAG	p.Gln620del	conservative_inframe_deletion	6/6	ENST00000171111.10	NP_987096.1	Q14145A0A024R7C0
KEAP1	NM_012289.4 linkuse as main transcript	c.1858_1860delCAG	p.Gln620del	conservative_inframe_deletion	6/6		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.1858_1860delCAG	p.Gln620del	conservative_inframe_deletion	6/6	1	NM_203500.2	ENSP00000171111.4		Q14145

Frequencies

GnomAD3 genomes

AF:

0.00197

AC:

300

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00264

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00344

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00213

AC:

535

AN:

251004

Hom.:

AF XY:

0.00220

AC XY:

298

AN XY:

135612

show subpopulations

Gnomad AFR exome

AF:

0.000738

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00296

Gnomad NFE exome

AF:

0.00400

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.00346

AC:

5065

AN:

1461836

Hom.:

AF XY:

0.00338

AC XY:

2460

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00301

Gnomad4 NFE exome

AF:

0.00429

Gnomad4 OTH exome

AF:

0.00174

GnomAD4 genome

AF:

0.00197

AC:

300

AN:

152236

Hom.:

Cov.:

AF XY:

0.00189

AC XY:

141

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.000794

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00264

Gnomad4 NFE

AF:

0.00344

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000581

Hom.:

Bravo

AF:

0.00181

EpiCase

AF:

0.00262

EpiControl

AF:

0.00344

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over