5-93583436-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005654.6(NR2F1):c.-1588T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0201 in 152,018 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (51 hom., cov: 30)
  • Exomes 𝑓: 0.032 (0 hom.)
• Consequence: NR2F1 NM_005654.6 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0710

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=-0.95).
• BP6: Variant 5-93583436-T-C is Benign according to our data. Variant chr5-93583436-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1200196.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR2F1	NM_005654.6	c.-1588T>C		5_prime_UTR_variant	1/3	ENST00000327111.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR2F1	ENST00000327111.8	c.-1588T>C		5_prime_UTR_variant	1/3	1	NM_005654.6	P1

Frequencies

GnomAD3 genomes AF: 0.0201 AC: 3047 AN: 151776 Hom.: 51 Cov.: 30

Gnomad AFR AF: 0.00482

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0153

Gnomad ASJ AF: 0.0421

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0592

Gnomad FIN AF: 0.0193

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0283

Gnomad OTH AF: 0.0168

GnomAD4 exome AF: 0.0323 AC: 4 AN: 124 Hom.: 0 Cov.: 0 AF XY: 0.0417 AC XY: 3 AN XY: 72

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0227

Gnomad4 NFE exome AF: 0.0227

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0200 AC: 3045 AN: 151894 Hom.: 51 Cov.: 30 AF XY: 0.0204 AC XY: 1515 AN XY: 74270

Gnomad4 AFR AF: 0.00481

Gnomad4 AMR AF: 0.0153

Gnomad4 ASJ AF: 0.0421

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0593

Gnomad4 FIN AF: 0.0193

Gnomad4 NFE AF: 0.0283

Gnomad4 OTH AF: 0.0171

Alfa AF: 0.0218 Hom.: 6

Bravo AF: 0.0179

Asia WGS AF: 0.0260 AC: 91 AN: 3478

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 29, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	12
Dann	Benign	0.69

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: rs76981368; hg19: chr5-92919142; COSMIC: COSV59067924; COSMIC: COSV59067924;