rs10497511

Variant names:

• chr2-177254568-G-A
• rs10497511
• NM_006164.5:c.45+9964C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-177254568-G-A
• chr2-177254568-G-C

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+9964C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.884 in 152,174 control chromosomes in the GnomAD database, including 59,664 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 (59664 hom., cov: 31)
• Consequence: NFE2L2 NM_006164.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.429
• Publications: 12 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFE2L2	NM_006164.5	c.45+9964C>T		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+9964C>T		intron_variant	Intron 1 of 4	1	NM_006164.5	ENSP00000380252.3

Frequencies

GnomAD3 genomes AF: 0.884 AC: 134470 AN: 152056 Hom.: 59604 Cov.: 31

Gnomad AFR AF: 0.926

Gnomad AMI AF: 0.895

Gnomad AMR AF: 0.855

Gnomad ASJ AF: 0.879

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.847

Gnomad FIN AF: 0.848

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.884

Gnomad OTH AF: 0.893

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

GnomAD4 genome AF: 0.884 AC: 134584 AN: 152174 Hom.: 59664 Cov.: 31 AF XY: 0.881 AC XY: 65540 AN XY: 74398

African (AFR) AF: 0.926 AC: 38441 AN: 41520

American (AMR) AF: 0.854 AC: 13064 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.879 AC: 3050 AN: 3470

East Asian (EAS) AF: 0.752 AC: 3885 AN: 5168

South Asian (SAS) AF: 0.847 AC: 4083 AN: 4820

European-Finnish (FIN) AF: 0.848 AC: 8975 AN: 10578

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

European-Non Finnish (NFE) AF: 0.884 AC: 60124 AN: 68008

Other (OTH) AF: 0.894 AC: 1888 AN: 2112

Alfa AF: 0.846 Hom.: 2622

Bravo AF: 0.885

Asia WGS AF: 0.835 AC: 2907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.45
DANN	Benign	0.58
PhyloP100		-0.43
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: rs10497511; hg19: chr2-178119296;