chr5-93585071-C-G

Variant names:

• chr5-93585071-C-G
• rs780151168
• NM_005654.6:c.48C>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_005654.6(NR2F1):​c.48C>G​(p.Ala16Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000113 in 885,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A16A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: NR2F1 NM_005654.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.232
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP7: Synonymous conserved (PhyloP=0.232 with no splicing effect.

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.48C>G	p.Ala16Ala	synonymous	Exon 1 of 3	NP_005645.1	P10589
	NR2F1-AS1	NR_186215.1		n.206+313G>C		intron	N/A
	NR2F1-AS1	NR_186216.1		n.261+258G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR2F1	ENST00000327111.8	TSL:1 MANE Select	c.48C>G	p.Ala16Ala	synonymous	Exon 1 of 3	ENSP00000325819.3	P10589
	NR2F1	ENST00000615873.2	TSL:1	c.48C>G	p.Ala16Ala	synonymous	Exon 1 of 4	ENSP00000481517.1	F1DAL9
	NR2F1	ENST00000647447.1		c.48C>G	p.Ala16Ala	synonymous	Exon 1 of 4	ENSP00000495740.1	F1DAL7

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000113 AC: 1 AN: 885132 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 417708

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 17030

American (AMR) AF: 0.00 AC: 0 AN: 4716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6102

East Asian (EAS) AF: 0.00 AC: 0 AN: 6014

South Asian (SAS) AF: 0.00 AC: 0 AN: 20174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2756

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3368

European-Non Finnish (NFE) AF: 0.00000126 AC: 1 AN: 795396

Other (OTH) AF: 0.00 AC: 0 AN: 29576

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	14
DANN	Benign	0.84
PhyloP100		0.23
PromoterAI		-0.024	Neutral

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: rs780151168; hg19: chr5-92920777;