2-177269949-A-G

Position:

• chr2-177269949-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000699346.1(NFE2L2):​c.183+26598T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 152,080 control chromosomes in the GnomAD database, including 29,014 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 0.61 (29014 hom., cov: 32)
• Consequence: NFE2L2 ENST00000699346.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFE2L2	ENST00000464747.5	c.-3-35678T>C		intron_variant		2		P4
NFE2L2	ENST00000586532.6	c.43-35678T>C		intron_variant		5
NFE2L2	ENST00000588123.2	c.-4+13651T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92382 AN: 151962 Hom.: 28970 Cov.: 32

Gnomad AFR AF: 0.768

Gnomad AMI AF: 0.697

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.645

Gnomad SAS AF: 0.693

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.564

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

GnomAD4 genome AF: 0.608 AC: 92476 AN: 152080 Hom.: 29014 Cov.: 32 AF XY: 0.613 AC XY: 45557 AN XY: 74334

Gnomad4 AFR AF: 0.768

Gnomad4 AMR AF: 0.597

Gnomad4 ASJ AF: 0.507

Gnomad4 EAS AF: 0.645

Gnomad4 SAS AF: 0.693

Gnomad4 FIN AF: 0.560

Gnomad4 NFE AF: 0.517

Gnomad4 OTH AF: 0.568

Alfa AF: 0.534 Hom.: 36308

Bravo AF: 0.615

Asia WGS AF: 0.698 AC: 2428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.5
DANN	Benign	0.59

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6433657; hg19: chr2-178134677;