chr5-93585185-C-A

Variant names:

• chr5-93585185-C-A
• rs557800691
• NM_005654.6:c.162C>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The ENST00000615873.2(NR2F1):​c.87C>A​(p.Thr29Thr) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00212 in 1,515,938 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T29T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.011 (28 hom., cov: 30)
  • Exomes 𝑓: 0.0011 (30 hom.)
• Consequence: NR2F1 ENST00000615873.2 splice_region, synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.17
• Publications: 0 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 5-93585185-C-A is Benign according to our data. Variant chr5-93585185-C-A is described in ClinVar as Benign. ClinVar VariationId is 381438.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.17 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0111 (1665/149744) while in subpopulation AFR AF = 0.0384 (1580/41186). AF 95% confidence interval is 0.0368. There are 28 homozygotes in GnomAd4. There are 778 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 28 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000615873.2. 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.162C>A	p.Thr54Thr	synonymous	Exon 1 of 3	NP_005645.1	P10589
	NR2F1-AS1	NR_186215.1		n.206+199G>T		intron	N/A
	NR2F1-AS1	NR_186216.1		n.261+144G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR2F1	ENST00000327111.8	TSL:1 MANE Select	c.162C>A	p.Thr54Thr	synonymous	Exon 1 of 3	ENSP00000325819.3	P10589
	NR2F1	ENST00000615873.2	TSL:1	c.87C>A	p.Thr29Thr	splice_region synonymous	Exon 2 of 4	ENSP00000481517.1	F1DAL9
	NR2F1	ENST00000647447.1		c.85-76C>A		intron	N/A	ENSP00000495740.1	F1DAL7

Frequencies

GnomAD3 genomes AF: 0.0111 AC: 1663 AN: 149638 Hom.: 28 Cov.: 30

Gnomad AFR AF: 0.0384

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00392

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000193

Gnomad OTH AF: 0.00630

GnomAD2 exomes AF: 0.00206 AC: 256 AN: 124488 AF XY: 0.00184

Gnomad AFR exome AF: 0.0346

Gnomad AMR exome AF: 0.00172

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000664

Gnomad OTH exome AF: 0.000261

GnomAD4 exome AF: 0.00114 AC: 1555 AN: 1366194 Hom.: 30 Cov.: 32 AF XY: 0.00101 AC XY: 681 AN XY: 672644

African (AFR) AF: 0.0409 AC: 1259 AN: 30746

American (AMR) AF: 0.00190 AC: 66 AN: 34784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23712

East Asian (EAS) AF: 0.00 AC: 0 AN: 34932

South Asian (SAS) AF: 0.000156 AC: 12 AN: 77000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37766

Middle Eastern (MID) AF: 0.00251 AC: 12 AN: 4786

European-Non Finnish (NFE) AF: 0.0000760 AC: 81 AN: 1065946

Other (OTH) AF: 0.00221 AC: 125 AN: 56522

GnomAD4 genome AF: 0.0111 AC: 1665 AN: 149744 Hom.: 28 Cov.: 30 AF XY: 0.0106 AC XY: 778 AN XY: 73124

African (AFR) AF: 0.0384 AC: 1580 AN: 41186

American (AMR) AF: 0.00392 AC: 59 AN: 15062

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3450

East Asian (EAS) AF: 0.00 AC: 0 AN: 5058

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000193 AC: 13 AN: 67360

Other (OTH) AF: 0.00623 AC: 13 AN: 2086

Alfa AF: 0.00475 Hom.: 2

Bravo AF: 0.0121

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	15
DANN	Benign	0.97
PhyloP100		1.2
PromoterAI		0.044	Neutral
Mutation Taster		=98/2	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: rs557800691; hg19: chr5-92920891;