2-177255663-T-C

Variant names:

• chr2-177255663-T-C
• rs10188193
• NM_006164.5:c.45+8869A>G

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+8869A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.88 in 152,156 control chromosomes in the GnomAD database, including 59,037 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 0.88 (59037 hom., cov: 30)
• Consequence: NFE2L2 NM_006164.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.16
• Publications: 2 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFE2L2	NM_006164.5	c.45+8869A>G		intron_variant	Intron 1 of 4	ENST00000397062.8	NP_006155.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFE2L2	ENST00000397062.8	c.45+8869A>G		intron_variant	Intron 1 of 4	1	NM_006164.5	ENSP00000380252.3

Frequencies

GnomAD3 genomes AF: 0.880 AC: 133780 AN: 152038 Hom.: 58978 Cov.: 30

Gnomad AFR AF: 0.910

Gnomad AMI AF: 0.895

Gnomad AMR AF: 0.853

Gnomad ASJ AF: 0.879

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.846

Gnomad FIN AF: 0.849

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.884

Gnomad OTH AF: 0.887

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

GnomAD4 genome AF: 0.880 AC: 133894 AN: 152156 Hom.: 59037 Cov.: 30 AF XY: 0.877 AC XY: 65208 AN XY: 74374

African (AFR) AF: 0.910 AC: 37781 AN: 41514

American (AMR) AF: 0.852 AC: 13034 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.879 AC: 3050 AN: 3468

East Asian (EAS) AF: 0.755 AC: 3898 AN: 5166

South Asian (SAS) AF: 0.846 AC: 4078 AN: 4820

European-Finnish (FIN) AF: 0.849 AC: 8973 AN: 10574

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.884 AC: 60132 AN: 68006

Other (OTH) AF: 0.887 AC: 1874 AN: 2112

Alfa AF: 0.876 Hom.: 6806

Bravo AF: 0.880

Asia WGS AF: 0.834 AC: 2904 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.4
DANN	Benign	0.44
PhyloP100		-2.2
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: rs10188193; hg19: chr2-178120391;