5-93585185-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The ENST00000615873.2(NR2F1):​c.87C>T​(p.Thr29Thr) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. T29T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: NR2F1 ENST00000615873.2 splice_region, synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 5-93585185-C-T is Benign according to our data. Variant chr5-93585185-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 507591.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.17 with no splicing effect.

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>T	p.Thr54Thr	synonymous	Exon 1 of 3	NP_005645.1	P10589
	NR2F1-AS1	NR_186215.1		n.206+199G>A		intron	N/A
	NR2F1-AS1	NR_186216.1		n.261+144G>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.162C>T	p.Thr54Thr	synonymous	Exon 1 of 3	ENSP00000325819.3	P10589
	NR2F1	ENST00000615873.2	TSL:1	c.87C>T	p.Thr29Thr	splice_region synonymous	Exon 2 of 4	ENSP00000481517.1	F1DAL9
	NR2F1	ENST00000647447.1		c.85-76C>T		intron	N/A	ENSP00000495740.1	F1DAL7

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

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	-0.39
CADD	Benign	16
DANN	Uncertain	0.99
PhyloP100		1.2
PromoterAI		0.046	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;