12-54293448-A-G

Variant names:

• chr12-54293448-A-G
• rs10506328
• NM_001136023.3:c.115-67T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001136023.3(NFE2):​c.115-67T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NFE2 NM_001136023.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.302
• Publications: 48 publications found

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]

NFE2 Gene-Disease associations (from GenCC):

• thrombocytopenia

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ENSG00000258344 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136023.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFE2	NM_001136023.3	MANE Select	c.115-67T>C		intron	N/A	NP_001129495.1	Q16621
	NFE2	NM_001261461.2		c.115-67T>C		intron	N/A	NP_001248390.1	A8K3E0
	NFE2	NM_001400365.1		c.115-67T>C		intron	N/A	NP_001387294.1	A8K3E0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFE2	ENST00000435572.7	TSL:1 MANE Select	c.115-67T>C		intron	N/A	ENSP00000397185.2	Q16621
	NFE2	ENST00000312156.8	TSL:1	c.115-67T>C		intron	N/A	ENSP00000312436.4	Q16621
	NFE2	ENST00000540264.2	TSL:1	c.115-67T>C		intron	N/A	ENSP00000439120.2	Q16621

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1232360 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 595666

African (AFR) AF: 0.00 AC: 0 AN: 27870

American (AMR) AF: 0.00 AC: 0 AN: 23380

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16922

East Asian (EAS) AF: 0.00 AC: 0 AN: 34646

South Asian (SAS) AF: 0.00 AC: 0 AN: 43044

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43964

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4828

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 987882

Other (OTH) AF: 0.00 AC: 0 AN: 49824

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.6
DANN	Benign	0.74
PhyloP100		-0.30

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

Other links and lift over

dbSNP: rs10506328; hg19: chr12-54687232;