Genetic Variant NR2F1:c.-1729_-1728delCT (chr5-93583271-GTC-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_005654.6(NR2F1):c.-1729_-1728delCT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00603 in 144,392 control chromosomes in the GnomAD database, including 5 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0060 ( 5 hom., cov: 25)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NR2F1
NM_005654.6 5_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.887

Publications

0 publications found

Variant links:

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 links:

NR2F1-AS1 (HGNC:48622): (NR2F1 antisense RNA 1)

NR2F1-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00603 (870/144392) while in subpopulation AFR AF = 0.0143 (560/39260). AF 95% confidence interval is 0.0133. There are 5 homozygotes in GnomAd4. There are 440 alleles in the male GnomAd4 subpopulation. Median coverage is 25. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR2F1	NM_005654.6 link	c.-1729_-1728delCT		5_prime_UTR_variant	Exon 1 of 3	ENST00000327111.8	NP_005645.1	P10589

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR2F1	ENST00000327111.8 link	c.-1729_-1728delCT		5_prime_UTR_variant	Exon 1 of 3	1	NM_005654.6	ENSP00000325819.3		P10589

Frequencies

GnomAD3 genomes

AF:

0.00597

AC:

861

AN:

144328

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0141

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00330

Gnomad ASJ

AF:

0.00118

Gnomad EAS

AF:

0.00409

Gnomad SAS

AF:

0.00381

Gnomad FIN

AF:

0.00811

Gnomad MID

AF:

0.00680

Gnomad NFE

AF:

0.00202

Gnomad OTH

AF:

0.00563

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.00603

AC:

870

AN:

144392

Hom.:

Cov.:

AF XY:

0.00629

AC XY:

440

AN XY:

69988

show subpopulations

African (AFR)

AF:

0.0143

AC:

560

AN:

39260

American (AMR)

AF:

0.00330

AC:

AN:

14548

Ashkenazi Jewish (ASJ)

AF:

0.00118

AC:

AN:

3378

East Asian (EAS)

AF:

0.00431

AC:

AN:

4870

South Asian (SAS)

AF:

0.00405

AC:

AN:

4446

European-Finnish (FIN)

AF:

0.00811

AC:

AN:

8996

Middle Eastern (MID)

AF:

0.00746

AC:

AN:

268

European-Non Finnish (NFE)

AF:

0.00202

AC:

133

AN:

65760

Other (OTH)

AF:

0.00557

AC:

AN:

1974

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

122

153

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000473

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Oct 23, 2019

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.89

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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chr5-93583271-GTC-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over