2-177253424-C-T

Variant names:

• chr2-177253424-C-T
• rs1806649
• NM_006164.5:c.45+11108G>A

Variant summary

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

The NM_006164.5(NFE2L2):​c.45+11108G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,194 control chromosomes in the GnomAD database, including 2,861 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 0.17 (2861 hom., cov: 33)
• Consequence: NFE2L2 NM_006164.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.102
• Publications: 45 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: Illumina, ClinGen, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006164.5. 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
	NFE2L2	NM_006164.5	MANE Select	c.45+11108G>A		intron	N/A	NP_006155.2
	NFE2L2	NM_001145412.3		c.-4+9979G>A		intron	N/A	NP_001138884.1	Q16236-2
	NFE2L2	NM_001313900.1		c.-4+10105G>A		intron	N/A	NP_001300829.1	Q16236-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFE2L2	ENST00000397062.8	TSL:1 MANE Select	c.45+11108G>A		intron	N/A	ENSP00000380252.3	Q16236-1
	NFE2L2	ENST00000397063.9	TSL:1	c.-4+9979G>A		intron	N/A	ENSP00000380253.4	Q16236-2
	NFE2L2	ENST00000421929.6	TSL:1	c.-4+10105G>A		intron	N/A	ENSP00000412191.2	Q16236-2

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26195 AN: 152076 Hom.: 2861 Cov.: 33

Gnomad AFR AF: 0.0477

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.0813

Gnomad SAS AF: 0.0931

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.172 AC: 26192 AN: 152194 Hom.: 2861 Cov.: 33 AF XY: 0.166 AC XY: 12321 AN XY: 74412

African (AFR) AF: 0.0475 AC: 1974 AN: 41526

American (AMR) AF: 0.185 AC: 2826 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 835 AN: 3464

East Asian (EAS) AF: 0.0811 AC: 420 AN: 5178

South Asian (SAS) AF: 0.0938 AC: 453 AN: 4830

European-Finnish (FIN) AF: 0.171 AC: 1808 AN: 10602

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17248 AN: 67992

Other (OTH) AF: 0.215 AC: 454 AN: 2114

Alfa AF: 0.223 Hom.: 7663

Bravo AF: 0.170

Asia WGS AF: 0.0790 AC: 277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.1
DANN	Benign	0.64
PhyloP100		0.10
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: rs1806649; hg19: chr2-178118152;