chr5-93584991-C-T

Variant names:

• chr5-93584991-C-T
• rs372818347
• NM_005654.6:c.-33C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_005654.6(NR2F1):​c.-33C>T variant causes a 5 prime UTR premature start codon gain 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_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.24
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 2 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005654.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR2F1	NM_005654.6	MANE Select	c.-33C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	NP_005645.1	P10589
	NR2F1	NM_005654.6	MANE Select	c.-33C>T		5_prime_UTR	Exon 1 of 3	NP_005645.1	P10589
	NR2F1-AS1	NR_186215.1		n.206+393G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR2F1	ENST00000327111.8	TSL:1 MANE Select	c.-33C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000325819.3	P10589
	NR2F1	ENST00000327111.8	TSL:1 MANE Select	c.-33C>T		5_prime_UTR	Exon 1 of 3	ENSP00000325819.3	P10589
	NR2F1-AS1	ENST00000513055.2	TSL:5	n.216+393G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000946 AC: 138 AN: 145842 Hom.: 0 Cov.: 30

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

GnomAD2 exomes AF: 0.00105 AC: 5 AN: 4748 AF XY: 0.00146

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 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.: 2 Cov.: 18 AF XY: 0.00193 AC XY: 745 AN XY: 386632

African (AFR) AF: 0.000315 AC: 5 AN: 15878

American (AMR) AF: 0.000686 AC: 1 AN: 1458

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5232

East Asian (EAS) AF: 0.00 AC: 0 AN: 3924

South Asian (SAS) AF: 0.0000574 AC: 1 AN: 17426

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 768

Middle Eastern (MID) AF: 0.000315 AC: 1 AN: 3174

European-Non Finnish (NFE) AF: 0.00220 AC: 1674 AN: 759360

Other (OTH) AF: 0.000654 AC: 18 AN: 27528

GnomAD4 genome AF: 0.000946 AC: 138 AN: 145948 Hom.: 0 Cov.: 30 AF XY: 0.000817 AC XY: 58 AN XY: 71030

African (AFR) AF: 0.000245 AC: 10 AN: 40736

American (AMR) AF: 0.000271 AC: 4 AN: 14738

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3378

East Asian (EAS) AF: 0.00 AC: 0 AN: 4922

South Asian (SAS) AF: 0.00 AC: 0 AN: 4788

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8446

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.00187 AC: 123 AN: 65704

Other (OTH) AF: 0.000488 AC: 1 AN: 2048

Alfa AF: 0.000636 Hom.: 0

Bravo AF: 0.000979

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	20
DANN	Uncertain	0.99
PhyloP100		3.2
PromoterAI		-0.0036	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=300/0	polymorphism

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

Other links and lift over

dbSNP: rs372818347; hg19: chr5-92920697;