rs3743462

chr15-96327588-A-Gchr15-96327588-A-T

Variant summary

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

The ENST00000421109.6(NR2F2):c.43+1236A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,198 control chromosomes in the GnomAD database, including 2,522 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 0.16 (2522 hom., cov: 32)
• Consequence: NR2F2 ENST00000421109.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.12

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=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR2F2	NM_001145155.2	c.43+1236A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR2F2	ENST00000421109.6	c.43+1236A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23830 AN: 152080 Hom.: 2525 Cov.: 32

Gnomad AFR AF: 0.0608

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.142

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.157 AC: 23835 AN: 152198 Hom.: 2522 Cov.: 32 AF XY: 0.164 AC XY: 12182 AN XY: 74396

Gnomad4 AFR AF: 0.0608

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.504

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.143

Alfa AF: 0.157 Hom.: 2637

Bravo AF: 0.155

Asia WGS AF: 0.288 AC: 998 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	16
Dann	Benign	0.84

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3743462; hg19: chr15-96870817; COSMIC: COSV67683512; COSMIC: COSV67683512;