Variant 5-93584837-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005654.6(NR2F1):c.-187G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.027 in 157,960 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 94 hom., cov: 30)

Exomes 𝑓: 0.024 ( 7 hom. )

Consequence

NR2F1
NM_005654.6 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.795

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 5-93584837-G-A is Benign according to our data. Variant chr5-93584837-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 676347.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0273 (4040/148246) while in subpopulation NFE AF= 0.0432 (2875/66474). AF 95% confidence interval is 0.0419. There are 94 homozygotes in gnomad4. There are 1804 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High AC in GnomAd4 at 4040 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR2F1	NM_005654.6 link	c.-187G>A		5_prime_UTR_variant	1/3	ENST00000327111.8	NP_005645.1	P10589

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR2F1	ENST00000327111 link	c.-187G>A		5_prime_UTR_variant	1/3	1	NM_005654.6	ENSP00000325819.3		P10589

Frequencies

GnomAD3 genomes

AF:

0.0273

AC:

4044

AN:

148162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00795

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0255

Gnomad ASJ

AF:

0.0497

Gnomad EAS

AF:

0.000397

Gnomad SAS

AF:

0.0222

Gnomad FIN

AF:

0.0100

Gnomad MID

AF:

0.0425

Gnomad NFE

AF:

0.0433

Gnomad OTH

AF:

0.0255

GnomAD4 exome

AF:

0.0236

AC:

229

AN:

9714

Hom.:

Cov.:

AF XY:

0.0241

AC XY:

150

AN XY:

6216

show subpopulations

Gnomad4 AFR exome

AF:

0.00676

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0233

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0274

Gnomad4 FIN exome

AF:

0.00897

Gnomad4 NFE exome

AF:

0.0263

Gnomad4 OTH exome

AF:

0.0145

GnomAD4 genome

AF:

0.0273

AC:

4040

AN:

148246

Hom.:

Cov.:

AF XY:

0.0250

AC XY:

1804

AN XY:

72302

show subpopulations

Gnomad4 AFR

AF:

0.00793

Gnomad4 AMR

AF:

0.0254

Gnomad4 ASJ

AF:

0.0497

Gnomad4 EAS

AF:

0.000398

Gnomad4 SAS

AF:

0.0219

Gnomad4 FIN

AF:

0.0100

Gnomad4 NFE

AF:

0.0432

Gnomad4 OTH

AF:

0.0253

Alfa

AF:

0.0289

Hom.:

Bravo

AF:

0.0275

Asia WGS

AF:

0.0100

AC:

AN:

3150

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 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. -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

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