5-93583271-G-GTCTCTC

Variant names:

• chr5-93583271-G-GTCTCTC
• rs140194624
• NM_005654.6:c.-1733_-1728dupCTCTCT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B.

Score: -4 - Likely Benign

-4

BS1

The NM_005654.6(NR2F1):​c.-1733_-1728dupCTCTCT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000338 in 145,074 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00034 (1 hom., cov: 25)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NR2F1 NM_005654.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.887
• 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 -4 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000338 (49/145074) while in subpopulation EAS AF = 0.000411 (2/4872). AF 95% confidence interval is 0.000288. There are 1 homozygotes in GnomAd4. There are 16 alleles in the male GnomAd4 subpopulation. Median coverage is 25. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR2F1	NM_005654.6	c.-1733_-1728dupCTCTCT		5_prime_UTR_variant	Exon 1 of 3	ENST00000327111.8	NP_005645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR2F1	ENST00000327111.8	c.-1733_-1728dupCTCTCT		5_prime_UTR_variant	Exon 1 of 3	1	NM_005654.6	ENSP00000325819.3

Frequencies

GnomAD3 genomes AF: 0.000338 AC: 49 AN: 145002 Hom.: 1 Cov.: 25

Gnomad AFR AF: 0.000229

Gnomad AMI AF: 0.00785

Gnomad AMR AF: 0.000206

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000409

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000409

Gnomad OTH AF: 0.000510

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 26 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 20

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 20

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.000338 AC: 49 AN: 145074 Hom.: 1 Cov.: 25 AF XY: 0.000227 AC XY: 16 AN XY: 70336

African (AFR) AF: 0.000229 AC: 9 AN: 39354

American (AMR) AF: 0.000206 AC: 3 AN: 14588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3386

East Asian (EAS) AF: 0.000411 AC: 2 AN: 4872

South Asian (SAS) AF: 0.00 AC: 0 AN: 4450

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9270

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 268

European-Non Finnish (NFE) AF: 0.000409 AC: 27 AN: 66012

Other (OTH) AF: 0.000505 AC: 1 AN: 1982

Alfa AF: 0.0000676 Hom.: 43

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.89

Splicing

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

Other links and lift over

dbSNP: rs140194624; hg19: chr5-92918977;