rs16865105

Positions:

• chr2-177271901-A-C

Variant summary

Our verdict is Benign. Variant got -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: ENST00000699473.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.751

Genes affected

(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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000699473.1	n.4057T>G		non_coding_transcript_exon_variant	11/11

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

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.0833

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.199

Alfa AF: 0.217 Hom.: 1138

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16865105; hg19: chr2-178136629;