rs16865105

Variant names:

• chr2-177271901-A-C
• rs16865105
• ENST00000699473.1:n.4057T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000699473.1(ENSG00000213963):​n.4057T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,180 control chromosomes in the GnomAD database, including 3,851 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 0.22 (3851 hom., cov: 32)
• Consequence: ENSG00000213963 ENST00000699473.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.751
• Publications: 12 publications found

Genes affected

ENSG00000213963 (HGNC:):

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000213963	ENST00000699473.1	n.4057T>G		non_coding_transcript_exon_variant	Exon 11 of 11
NFE2L2	ENST00000699346.1	c.183+24646T>G		intron_variant	Intron 7 of 10			ENSP00000514321.1
NFE2L2	ENST00000586532.6	c.43-37630T>G		intron_variant	Intron 3 of 6	5		ENSP00000464920.2

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33137 AN: 152062 Hom.: 3848 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.0837

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.218 AC: 33146 AN: 152180 Hom.: 3851 Cov.: 32 AF XY: 0.215 AC XY: 16010 AN XY: 74410

African (AFR) AF: 0.262 AC: 10877 AN: 41506

American (AMR) AF: 0.158 AC: 2422 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 880 AN: 3468

East Asian (EAS) AF: 0.0833 AC: 433 AN: 5196

South Asian (SAS) AF: 0.198 AC: 955 AN: 4828

European-Finnish (FIN) AF: 0.220 AC: 2326 AN: 10592

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14308 AN: 67976

Other (OTH) AF: 0.199 AC: 421 AN: 2112

Alfa AF: 0.217 Hom.: 1432

Bravo AF: 0.218

Asia WGS AF: 0.118 AC: 410 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.4
DANN	Benign	0.24
PhyloP100		0.75
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs16865105; hg19: chr2-178136629;