2-177265345-T-C

Position:

• chr2-177265345-T-C

Variant summary

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

The ENST00000464747.5(NFE2L2):​c.-3-31074A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 199,732 control chromosomes in the GnomAD database, including 10,828 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 0.30 (7562 hom., cov: 33)
  • Exomes 𝑓: 0.36 (3266 hom.)
• Consequence: NFE2L2 ENST00000464747.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.177265345T>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFE2L2	ENST00000699346.1	c.184-31074A>G		intron_variant				ENSP00000514321.1
NFE2L2	ENST00000586532.6	c.43-31074A>G		intron_variant		5		ENSP00000464920.2
NFE2L2	ENST00000699265.1	c.43-31074A>G		intron_variant				ENSP00000514246.1

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45585 AN: 152010 Hom.: 7543 Cov.: 33

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.287

GnomAD4 exome AF: 0.359 AC: 17104 AN: 47604 Hom.: 3266 Cov.: 0 AF XY: 0.359 AC XY: 7978 AN XY: 22232

Gnomad4 AFR exome AF: 0.189

Gnomad4 AMR exome AF: 0.425

Gnomad4 ASJ exome AF: 0.258

Gnomad4 EAS exome AF: 0.570

Gnomad4 SAS exome AF: 0.551

Gnomad4 FIN exome AF: 0.367

Gnomad4 NFE exome AF: 0.323

Gnomad4 OTH exome AF: 0.326

GnomAD4 genome AF: 0.300 AC: 45620 AN: 152128 Hom.: 7562 Cov.: 33 AF XY: 0.310 AC XY: 23043 AN XY: 74354

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.401

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.521

Gnomad4 SAS AF: 0.492

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.292

Alfa AF: 0.307 Hom.: 922

Bravo AF: 0.292

Asia WGS AF: 0.528 AC: 1839 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	13
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs35652124; hg19: chr2-178130073; COSMIC: COSV67961672; COSMIC: COSV67961672;