rs10506328

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.302
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 UniProt
NFE2NM_001136023.3 linkuse as main transcriptc.115-67T>G intron_variant ENST00000435572.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NFE2ENST00000435572.7 linkuse as main transcriptc.115-67T>G intron_variant 1 NM_001136023.3 P1
ENST00000553061.1 linkuse as main transcriptn.545+16273A>C intron_variant, non_coding_transcript_variant 5

Frequencies

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs10506328; hg19: chr12-54687232; API