rs10930781

Variant names:

• chr2-177249904-A-G
• rs10930781
• NM_006164.5:c.45+14628T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-177249904-A-G
• chr2-177249904-A-T

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+14628T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.894 in 152,280 control chromosomes in the GnomAD database, including 60,931 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 0.89 (60931 hom., cov: 33)
• Consequence: NFE2L2 NM_006164.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 10 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=-0.92).
• 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+14628T>C		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+14628T>C		intron_variant	Intron 1 of 4	1	NM_006164.5	ENSP00000380252.3

Frequencies

GnomAD3 genomes AF: 0.893 AC: 135951 AN: 152162 Hom.: 60873 Cov.: 33

Gnomad AFR AF: 0.926

Gnomad AMI AF: 0.883

Gnomad AMR AF: 0.864

Gnomad ASJ AF: 0.893

Gnomad EAS AF: 0.747

Gnomad SAS AF: 0.890

Gnomad FIN AF: 0.853

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.898

Gnomad OTH AF: 0.905

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

GnomAD4 genome AF: 0.894 AC: 136067 AN: 152280 Hom.: 60931 Cov.: 33 AF XY: 0.890 AC XY: 66290 AN XY: 74450

African (AFR) AF: 0.926 AC: 38481 AN: 41558

American (AMR) AF: 0.864 AC: 13220 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.893 AC: 3101 AN: 3472

East Asian (EAS) AF: 0.747 AC: 3869 AN: 5178

South Asian (SAS) AF: 0.890 AC: 4299 AN: 4830

European-Finnish (FIN) AF: 0.853 AC: 9037 AN: 10592

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.898 AC: 61080 AN: 68034

Other (OTH) AF: 0.906 AC: 1912 AN: 2110

Alfa AF: 0.895 Hom.: 210543

Bravo AF: 0.893

Asia WGS AF: 0.843 AC: 2933 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.33
DANN	Benign	0.26
PhyloP100		-1.3
Mutation Taster		=97/3	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: rs10930781; hg19: chr2-178114632;