chr5-93593851-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005654.6(NR2F1):​c.*9C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000129 in 1,611,164 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00013 ( 2 hom. )

Consequence

NR2F1
NM_005654.6 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.48

Publications

1 publications found
Variant links:
Genes affected
NR2F1 (HGNC:7975): (nuclear receptor subfamily 2 group F member 1) The protein encoded by this gene is a nuclear hormone receptor and transcriptional regulator. The encoded protein acts as a homodimer and binds to 5'-AGGTCA-3' repeats. Defects in this gene are a cause of Bosch-Boonstra optic atrophy syndrome (BBOAS). [provided by RefSeq, Apr 2014]
NR2F1 Gene-Disease associations (from GenCC):
  • Bosch-Boonstra-Schaaf optic atrophy syndrome
    Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, ClinGen, Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
Variant 5-93593851-C-T is Benign according to our data. Variant chr5-93593851-C-T is described in CliVar as Benign. Clinvar id is 385015.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0000854 (13/152278) while in subpopulation SAS AF = 0.00124 (6/4826). AF 95% confidence interval is 0.000541. There are 0 homozygotes in GnomAd4. There are 7 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
BS2
High Homozygotes in GnomAdExome4 at 2 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NR2F1NM_005654.6 linkc.*9C>T 3_prime_UTR_variant Exon 3 of 3 ENST00000327111.8 NP_005645.1 P10589
NR2F1NM_001410754.1 linkc.*9C>T 3_prime_UTR_variant Exon 3 of 3 NP_001397683.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NR2F1ENST00000327111.8 linkc.*9C>T 3_prime_UTR_variant Exon 3 of 3 1 NM_005654.6 ENSP00000325819.3 P10589

Frequencies

GnomAD3 genomes
AF:
0.0000920
AC:
14
AN:
152160
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00124
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.000478
GnomAD2 exomes
AF:
0.000196
AC:
49
AN:
249734
AF XY:
0.000222
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000174
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000709
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000134
AC:
195
AN:
1458886
Hom.:
2
Cov.:
31
AF XY:
0.000165
AC XY:
120
AN XY:
725280
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33428
American (AMR)
AF:
0.000202
AC:
9
AN:
44638
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25944
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39652
South Asian (SAS)
AF:
0.00134
AC:
115
AN:
86040
European-Finnish (FIN)
AF:
0.0000188
AC:
1
AN:
53288
Middle Eastern (MID)
AF:
0.00156
AC:
9
AN:
5756
European-Non Finnish (NFE)
AF:
0.0000496
AC:
55
AN:
1109888
Other (OTH)
AF:
0.0000996
AC:
6
AN:
60252
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.489
Heterozygous variant carriers
0
11
22
32
43
54
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000854
AC:
13
AN:
152278
Hom.:
0
Cov.:
32
AF XY:
0.0000940
AC XY:
7
AN XY:
74450
show subpopulations
African (AFR)
AF:
0.0000241
AC:
1
AN:
41556
American (AMR)
AF:
0.0000654
AC:
1
AN:
15294
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5184
South Asian (SAS)
AF:
0.00124
AC:
6
AN:
4826
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10602
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.0000588
AC:
4
AN:
68024
Other (OTH)
AF:
0.000473
AC:
1
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.514
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0000825
Hom.:
0
Bravo
AF:
0.0000529

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Jun 07, 2018
Athena Diagnostics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Apr 10, 2020
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.52
CADD
Benign
13
DANN
Benign
0.87
PhyloP100
1.5
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs202006298; hg19: chr5-92929557; COSMIC: COSV100504559; COSMIC: COSV100504559; API