5-93585043-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 3P and 10B. PM2 PP2 BP4_Moderate BP6_Very_Strong

The NM_005654.6(NR2F1):c.20G>A(p.Ser7Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000029 in 1,033,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0000068 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: NR2F1 NM_005654.6 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.109

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 -7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, NR2F1
• BP4: Computational evidence support a benign effect (MetaRNN=0.21509069).
• BP6: Variant 5-93585043-G-A is Benign according to our data. Variant chr5-93585043-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1191570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR2F1	NM_005654.6	c.20G>A	p.Ser7Asn	missense_variant	1/3	ENST00000327111.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR2F1	ENST00000327111.8	c.20G>A	p.Ser7Asn	missense_variant	1/3	1	NM_005654.6	P1

Frequencies

GnomAD3 genomes AF: 0.00000683 AC: 1 AN: 146440 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000678

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000225 AC: 2 AN: 887420 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 418456

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000361

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000683 AC: 1 AN: 146440 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 71230

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000678

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000151

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 04, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 14, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
Cadd	Benign	21
Dann	Uncertain	0.98
DEOGEN2	Benign	0.13	T;T;.;T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.28	N
M_CAP	Pathogenic	0.80	D
MetaRNN	Benign	0.22	T;T;T;T
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	0.0	N;N;.;.
MutationTaster	Benign	0.98	N
PrimateAI	Pathogenic	0.93	D
Polyphen		0.0070	B;B;.;.
Vest4		0.087, 0.13
MutPred		0.11		Loss of phosphorylation at S7 (P = 0.0427);Loss of phosphorylation at S7 (P = 0.0427);Loss of phosphorylation at S7 (P = 0.0427);Loss of phosphorylation at S7 (P = 0.0427);
MVP		0.55
ClinPred		0.13	T
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
gMVP		0.20

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: rs1753203799; hg19: chr5-92920749;