12-54293448-A-C

Position:

• chr12-54293448-A-C

Variant summary

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

The NM_001136023.3(NFE2):​c.115-67T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 1,383,724 control chromosomes in the GnomAD database, including 329,763 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 0.76 (45023 hom., cov: 32)
  • Exomes 𝑓: 0.67 (284740 hom.)
• Consequence: NFE2 NM_001136023.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.302

Genes affected

NFE2 (HGNC:7780): (nuclear factor, erythroid 2) Enables several functions, including WW domain binding activity; identical protein binding activity; and protein N-terminus binding activity. Contributes to cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including labyrinthine layer blood vessel development; negative regulation of bone mineralization; and negative regulation of syncytium formation by plasma membrane fusion. Part of protein-DNA complex. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFE2	NM_001136023.3	c.115-67T>G		intron_variant		ENST00000435572.7	NP_001129495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFE2	ENST00000435572.7	c.115-67T>G		intron_variant		1	NM_001136023.3	ENSP00000397185	P1
	ENST00000553061.1	n.545+16273A>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.756 AC: 114899 AN: 152048 Hom.: 44953 Cov.: 32

Gnomad AFR AF: 0.937

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.883

Gnomad FIN AF: 0.746

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.718

GnomAD4 exome AF: 0.673 AC: 829408 AN: 1231558 Hom.: 284740 AF XY: 0.674 AC XY: 400965 AN XY: 595258

Gnomad4 AFR exome AF: 0.950

Gnomad4 AMR exome AF: 0.818

Gnomad4 ASJ exome AF: 0.589

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.877

Gnomad4 FIN exome AF: 0.745

Gnomad4 NFE exome AF: 0.639

Gnomad4 OTH exome AF: 0.703

GnomAD4 genome AF: 0.756 AC: 115030 AN: 152166 Hom.: 45023 Cov.: 32 AF XY: 0.764 AC XY: 56859 AN XY: 74394

Gnomad4 AFR AF: 0.938

Gnomad4 AMR AF: 0.755

Gnomad4 ASJ AF: 0.593

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.882

Gnomad4 FIN AF: 0.746

Gnomad4 NFE AF: 0.633

Gnomad4 OTH AF: 0.721

Alfa AF: 0.658 Hom.: 73664

Bravo AF: 0.764

Asia WGS AF: 0.942 AC: 3274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	9.3
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs10506328; hg19: chr12-54687232;