rs8113472

Variant names:

• chr19-10497388-C-A
• rs8113472
• NM_203500.2:c.639+2007G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-10497388-C-A
• chr19-10497388-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_203500.2(KEAP1):​c.639+2007G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,110 control chromosomes in the GnomAD database, including 1,072 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 0.11 (1072 hom., cov: 32)
• Consequence: KEAP1 NM_203500.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.396
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203500.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KEAP1	NM_203500.2	MANE Select	c.639+2007G>T		intron	N/A	NP_987096.1	Q14145
	KEAP1	NM_012289.4		c.639+2007G>T		intron	N/A	NP_036421.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KEAP1	ENST00000171111.10	TSL:1 MANE Select	c.639+2007G>T		intron	N/A	ENSP00000171111.4	Q14145
	KEAP1	ENST00000393623.6	TSL:1	c.639+2007G>T		intron	N/A	ENSP00000377245.1	Q14145
	KEAP1	ENST00000953686.1		c.639+2007G>T		intron	N/A	ENSP00000623745.1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16487 AN: 151992 Hom.: 1066 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0736

Gnomad ASJ AF: 0.0720

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0251

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0890

Gnomad OTH AF: 0.107

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.109 AC: 16516 AN: 152110 Hom.: 1072 Cov.: 32 AF XY: 0.107 AC XY: 7972 AN XY: 74356

African (AFR) AF: 0.176 AC: 7294 AN: 41474

American (AMR) AF: 0.0734 AC: 1121 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0720 AC: 250 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5186

South Asian (SAS) AF: 0.0251 AC: 121 AN: 4818

European-Finnish (FIN) AF: 0.126 AC: 1332 AN: 10576

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0890 AC: 6052 AN: 68000

Other (OTH) AF: 0.106 AC: 223 AN: 2110

Alfa AF: 0.0922 Hom.: 2368

Bravo AF: 0.111

Asia WGS AF: 0.0320 AC: 111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.86
DANN	Benign	0.76
PhyloP100		0.40
Mutation Taster		=100/0	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: rs8113472; hg19: chr19-10608064;