rs11545829

Variant names:

• chr19-10489289-G-A
• rs11545829
• NM_203500.2:c.1611C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-10489289-G-A
• chr19-10489289-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.263
• Publications: 22 publications found

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 Gene-Disease associations (from GenCC):

• goiter, multinodular 1, with or without Sertoli-Leydig cell tumors

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KEAP1	NM_203500.2	c.1611C>T	p.Tyr537Tyr	synonymous_variant	Exon 5 of 6	ENST00000171111.10	NP_987096.1
KEAP1	NM_012289.4	c.1611C>T	p.Tyr537Tyr	synonymous_variant	Exon 5 of 6		NP_036421.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KEAP1	ENST00000171111.10	c.1611C>T	p.Tyr537Tyr	synonymous_variant	Exon 5 of 6	1	NM_203500.2	ENSP00000171111.4

Frequencies

GnomAD3 genomes AF: 0.0204 AC: 3096 AN: 151938 Hom.: 265 Cov.: 31

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

GnomAD2 exomes AF: 0.0416 AC: 10465 AN: 251306 AF XY: 0.0390

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 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.: 33 AF XY: 0.0163 AC XY: 11861 AN XY: 727208

African (AFR) AF: 0.00798 AC: 267 AN: 33472

American (AMR) AF: 0.0818 AC: 3658 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00585 AC: 153 AN: 26134

East Asian (EAS) AF: 0.293 AC: 11617 AN: 39692

South Asian (SAS) AF: 0.0537 AC: 4633 AN: 86252

European-Finnish (FIN) AF: 0.00270 AC: 144 AN: 53418

Middle Eastern (MID) AF: 0.00539 AC: 31 AN: 5756

European-Non Finnish (NFE) AF: 0.000701 AC: 779 AN: 1111998

Other (OTH) AF: 0.0261 AC: 1575 AN: 60388

GnomAD4 genome AF: 0.0204 AC: 3109 AN: 152056 Hom.: 266 Cov.: 31 AF XY: 0.0229 AC XY: 1702 AN XY: 74322

African (AFR) AF: 0.00800 AC: 332 AN: 41522

American (AMR) AF: 0.0512 AC: 779 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.00548 AC: 19 AN: 3468

East Asian (EAS) AF: 0.296 AC: 1522 AN: 5134

South Asian (SAS) AF: 0.0671 AC: 323 AN: 4814

European-Finnish (FIN) AF: 0.00132 AC: 14 AN: 10596

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00110 AC: 75 AN: 67988

Other (OTH) AF: 0.0209 AC: 44 AN: 2104

Alfa AF: 0.0105 Hom.: 236

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
PhyloP100		-0.26
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11545829; hg19: chr19-10599965; COSMIC: COSV50266753; COSMIC: COSV50266753;