5-93584837-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.795

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

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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 GnomAd at 4044 AD gene.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR2F1	ENST00000327111.8	c.-187G>A		5_prime_UTR_variant	1/3	1	NM_005654.6	P1

Frequencies

GnomAD3 genomes AF: 0.0273 AC: 4044 AN: 148162 Hom.: 94 Cov.: 30

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.: 7 Cov.: 2 AF XY: 0.0241 AC XY: 150 AN XY: 6216

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.: 94 Cov.: 30 AF XY: 0.0250 AC XY: 1804 AN XY: 72302

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.: 13

Bravo AF: 0.0275

Asia WGS AF: 0.0100 AC: 32 AN: 3150

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	16
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

Other links and lift over

dbSNP: rs866080178; hg19: chr5-92920543;