2-177255584-T-G

Variant names:

• chr2-177255584-T-G
• rs10188107
• NM_006164.5:c.45+8948A>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+8948A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.885 in 152,044 control chromosomes in the GnomAD database, including 59,646 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 (59646 hom., cov: 30)
• Consequence: NFE2L2 NM_006164.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14
• Publications: 3 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.918 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFE2L2	NM_006164.5	MANE Select	c.45+8948A>C		intron	N/A	NP_006155.2
	NFE2L2	NM_001145412.3		c.-4+7819A>C		intron	N/A	NP_001138884.1
	NFE2L2	NM_001313900.1		c.-4+7945A>C		intron	N/A	NP_001300829.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFE2L2	ENST00000397062.8	TSL:1 MANE Select	c.45+8948A>C		intron	N/A	ENSP00000380252.3
	NFE2L2	ENST00000397063.9	TSL:1	c.-4+7819A>C		intron	N/A	ENSP00000380253.4
	NFE2L2	ENST00000421929.6	TSL:1	c.-4+7945A>C		intron	N/A	ENSP00000412191.2

Frequencies

GnomAD3 genomes AF: 0.885 AC: 134390 AN: 151926 Hom.: 59586 Cov.: 30

Gnomad AFR AF: 0.926

Gnomad AMI AF: 0.895

Gnomad AMR AF: 0.855

Gnomad ASJ AF: 0.879

Gnomad EAS AF: 0.754

Gnomad SAS AF: 0.846

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: 0.885 AC: 134504 AN: 152044 Hom.: 59646 Cov.: 30 AF XY: 0.881 AC XY: 65473 AN XY: 74300

African (AFR) AF: 0.926 AC: 38410 AN: 41470

American (AMR) AF: 0.855 AC: 13068 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.879 AC: 3048 AN: 3468

East Asian (EAS) AF: 0.754 AC: 3891 AN: 5162

South Asian (SAS) AF: 0.846 AC: 4063 AN: 4804

European-Finnish (FIN) AF: 0.848 AC: 8951 AN: 10554

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

European-Non Finnish (NFE) AF: 0.884 AC: 60112 AN: 67980

Other (OTH) AF: 0.893 AC: 1887 AN: 2112

Alfa AF: 0.857 Hom.: 3124

Bravo AF: 0.886

Asia WGS AF: 0.835 AC: 2908 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.5
DANN	Benign	0.31
PhyloP100		-2.1
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: rs10188107; hg19: chr2-178120312;