chr2-177268260-G-T

Variant names:

• chr2-177268260-G-T
• rs2364725
• ENST00000699346.1:c.183+28287C>A

Variant summary

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

The ENST00000699346.1(NFE2L2):​c.183+28287C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 152,072 control chromosomes in the GnomAD database, including 23,146 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 0.55 (23146 hom., cov: 32)
• Consequence: NFE2L2 ENST00000699346.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.426
• Publications: 15 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.669 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+28287C>A		intron_variant	Intron 7 of 10			ENSP00000514321.1
NFE2L2	ENST00000586532.6	c.43-33989C>A		intron_variant	Intron 3 of 6	5		ENSP00000464920.2
NFE2L2	ENST00000699265.1	c.43-33989C>A		intron_variant	Intron 5 of 8			ENSP00000514246.1

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83710 AN: 151954 Hom.: 23115 Cov.: 32

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.699

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.551 AC: 83783 AN: 152072 Hom.: 23146 Cov.: 32 AF XY: 0.557 AC XY: 41416 AN XY: 74330

African (AFR) AF: 0.581 AC: 24086 AN: 41462

American (AMR) AF: 0.567 AC: 8667 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1754 AN: 3470

East Asian (EAS) AF: 0.607 AC: 3147 AN: 5184

South Asian (SAS) AF: 0.689 AC: 3320 AN: 4820

European-Finnish (FIN) AF: 0.562 AC: 5940 AN: 10572

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.515 AC: 34991 AN: 67958

Other (OTH) AF: 0.512 AC: 1082 AN: 2112

Alfa AF: 0.537 Hom.: 12676

Bravo AF: 0.549

Asia WGS AF: 0.657 AC: 2287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.27
DANN	Benign	0.56
PhyloP100		-0.43
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: rs2364725; hg19: chr2-178132988;