Variant chr5-93584991-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_005654.6(NR2F1):c.-33C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00187 in 980,696 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00095 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0020 ( 2 hom. )

Consequence

NR2F1
NM_005654.6 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.24

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 links:

NR2F1-AS1 (HGNC:48622): (NR2F1 antisense RNA 1)

NR2F1-AS1 links:

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=-0.35).

BP6

Variant 5-93584991-C-T is Benign according to our data. Variant chr5-93584991-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 380104.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000946 (138/145948) while in subpopulation NFE AF= 0.00187 (123/65704). AF 95% confidence interval is 0.0016. There are 0 homozygotes in gnomad4. There are 58 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High AC in GnomAd4 at 138 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR2F1	NM_005654.6 linkuse as main transcript	c.-33C>T		5_prime_UTR_variant	1/3	ENST00000327111.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR2F1	ENST00000327111.8 linkuse as main transcript	c.-33C>T		5_prime_UTR_variant	1/3	1	NM_005654.6	P1

Frequencies

GnomAD3 genomes

AF:

0.000946

AC:

138

AN:

145842

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000246

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000272

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00187

Gnomad OTH

AF:

0.000494

GnomAD3 exomes

AF:

0.00105

AC:

AN:

4748

Hom.:

AF XY:

0.00146

AC XY:

AN XY:

2748

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00249

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00120

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00204

AC:

1700

AN:

834748

Hom.:

Cov.:

AF XY:

0.00193

AC XY:

745

AN XY:

386632

show subpopulations

Gnomad4 AFR exome

AF:

0.000315

Gnomad4 AMR exome

AF:

0.000686

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000574

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00220

Gnomad4 OTH exome

AF:

0.000654

GnomAD4 genome

AF:

0.000946

AC:

138

AN:

145948

Hom.:

Cov.:

AF XY:

0.000817

AC XY:

AN XY:

71030

show subpopulations

Gnomad4 AFR

AF:

0.000245

Gnomad4 AMR

AF:

0.000271

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00187

Gnomad4 OTH

AF:

0.000488

Alfa

AF:

0.000636

Hom.:

Bravo

AF:

0.000979

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 23, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over