15-96340092-G-T

Variant names:

• chr15-96340092-G-T
• rs11045
• NM_021005.4:c.*2470G>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021005.4(NR2F2):​c.*2470G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 152,036 control chromosomes in the GnomAD database, including 19,996 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.44 (19996 hom., cov: 32)
  • Exomes 𝑓: 0.20 (0 hom.)
• Consequence: NR2F2 NM_021005.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.619

Genes affected

NR2F2 (HGNC:7976): (nuclear receptor subfamily 2 group F member 2) This gene encodes a member of the steroid thyroid hormone superfamily of nuclear receptors. The encoded protein is a ligand inducible transcription factor that is involved in the regulation of many different genes. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR2F2	NM_021005.4	c.*2470G>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000394166.8	NP_066285.1
NR2F2	NM_001145155.2	c.*2470G>T		3_prime_UTR_variant	Exon 3 of 3		NP_001138627.1
NR2F2	NM_001145156.1	c.*2470G>T		3_prime_UTR_variant	Exon 3 of 3		NP_001138628.1
NR2F2	NM_001145157.2	c.*2470G>T		3_prime_UTR_variant	Exon 3 of 3		NP_001138629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR2F2	ENST00000394166.8	c.*2470G>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_021005.4	ENSP00000377721.3
NR2F2	ENST00000394171.6	c.*2470G>T		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000377726.2

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66656 AN: 151908 Hom.: 19923 Cov.: 32

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.405

GnomAD4 exome AF: 0.200 AC: 2 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 1 AN XY: 6

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.167

GnomAD4 genome AF: 0.439 AC: 66800 AN: 152026 Hom.: 19996 Cov.: 32 AF XY: 0.445 AC XY: 33032 AN XY: 74284

Gnomad4 AFR AF: 0.828

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.717

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.411

Alfa AF: 0.277 Hom.: 7987

Bravo AF: 0.475

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Benign	0.87

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

Publications

LitVar

Other links and lift over

dbSNP: rs11045; hg19: chr15-96883321;