5-93583271-GTC-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_005654.6(NR2F1):c.-1729_-1728del 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. Variant has been reported in ClinVar as Likely benign (★).

• 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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.887

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

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 5-93583271-GTC-G is Benign according to our data. Variant chr5-93583271-GTC-G is described in ClinVar as [Likely_benign]. Clinvar id is 1186466.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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 male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.
• BS2: High AC in GnomAd at 861 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR2F1	NM_005654.6	c.-1729_-1728del		5_prime_UTR_variant	1/3	ENST00000327111.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR2F1	ENST00000327111.8	c.-1729_-1728del		5_prime_UTR_variant	1/3	1	NM_005654.6	P1

Frequencies

GnomAD3 genomes AF: 0.00597 AC: 861 AN: 144328 Hom.: 5 Cov.: 25

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: 0 AN: 26 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 20

Gnomad4 ASJ exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00603 AC: 870 AN: 144392 Hom.: 5 Cov.: 25 AF XY: 0.00629 AC XY: 440 AN XY: 69988

Gnomad4 AFR AF: 0.0143

Gnomad4 AMR AF: 0.00330

Gnomad4 ASJ AF: 0.00118

Gnomad4 EAS AF: 0.00431

Gnomad4 SAS AF: 0.00405

Gnomad4 FIN AF: 0.00811

Gnomad4 NFE AF: 0.00202

Gnomad4 OTH AF: 0.00557

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 23, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs140194624; hg19: chr5-92918977;