rs6433657

Variant names:

• chr2-177269949-A-G
• rs6433657
• ENST00000699346.1:c.183+26598T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-177269949-A-G
• chr2-177269949-A-T

Variant summary

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

The ENST00000699346.1(NFE2L2):​c.183+26598T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 152,080 control chromosomes in the GnomAD database, including 29,014 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 0.61 (29014 hom., cov: 32)
• Consequence: NFE2L2 ENST00000699346.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500
• Publications: 7 publications found

Genes affected

NFE2L2 (HGNC:7782): (NFE2 like bZIP transcription factor 2) This gene encodes a transcription factor which is a member of a small family of basic leucine zipper (bZIP) proteins. The encoded transcription factor regulates genes which contain antioxidant response elements (ARE) in their promoters; many of these genes encode proteins involved in response to injury and inflammation which includes the production of free radicals. Multiple transcript variants encoding different isoforms have been characterized for this gene. [provided by RefSeq, Sep 2015]

NFE2L2 Gene-Disease associations (from GenCC):

• immunodeficiency, developmental delay, and hypohomocysteinemia

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Illumina, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFE2L2	ENST00000699346.1	c.183+26598T>C		intron_variant	Intron 7 of 10			ENSP00000514321.1
NFE2L2	ENST00000586532.6	c.43-35678T>C		intron_variant	Intron 3 of 6	5		ENSP00000464920.2
NFE2L2	ENST00000699265.1	c.43-35678T>C		intron_variant	Intron 5 of 8			ENSP00000514246.1

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92382 AN: 151962 Hom.: 28970 Cov.: 32

Gnomad AFR AF: 0.768

Gnomad AMI AF: 0.697

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.645

Gnomad SAS AF: 0.693

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.564

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

GnomAD4 genome AF: 0.608 AC: 92476 AN: 152080 Hom.: 29014 Cov.: 32 AF XY: 0.613 AC XY: 45557 AN XY: 74334

African (AFR) AF: 0.768 AC: 31891 AN: 41506

American (AMR) AF: 0.597 AC: 9111 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1761 AN: 3470

East Asian (EAS) AF: 0.645 AC: 3337 AN: 5176

South Asian (SAS) AF: 0.693 AC: 3337 AN: 4818

European-Finnish (FIN) AF: 0.560 AC: 5912 AN: 10552

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.517 AC: 35121 AN: 67986

Other (OTH) AF: 0.568 AC: 1198 AN: 2110

Alfa AF: 0.548 Hom.: 89663

Bravo AF: 0.615

Asia WGS AF: 0.698 AC: 2428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.5
DANN	Benign	0.59
PhyloP100		0.0050
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6433657; hg19: chr2-178134677;