15-96335065-A-G

Position:

• chr15-96335065-A-G

Variant summary

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

The NM_021005.4(NR2F2):​c.970+462A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 152,242 control chromosomes in the GnomAD database, including 14,770 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 0.39 (14770 hom., cov: 34)
• Consequence: NR2F2 NM_021005.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.92

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=-0.48).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR2F2	NM_021005.4	c.970+462A>G		intron_variant		ENST00000394166.8	NP_066285.1
NR2F2	NM_001145155.2	c.571+462A>G		intron_variant			NP_001138627.1
NR2F2	NM_001145156.1	c.511+462A>G		intron_variant			NP_001138628.1
NR2F2	NM_001145157.2	c.511+462A>G		intron_variant			NP_001138629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR2F2	ENST00000394166.8	c.970+462A>G		intron_variant		1	NM_021005.4	ENSP00000377721.3
NR2F2	ENST00000421109.6	c.571+462A>G		intron_variant		1		ENSP00000401674.2
NR2F2	ENST00000453270.2	c.511+462A>G		intron_variant		1		ENSP00000389853.2
NR2F2	ENST00000394171.6	c.511+462A>G		intron_variant		2		ENSP00000377726.2

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59580 AN: 152126 Hom.: 14722 Cov.: 34

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.392 AC: 59688 AN: 152242 Hom.: 14770 Cov.: 34 AF XY: 0.393 AC XY: 29278 AN XY: 74434

Gnomad4 AFR AF: 0.693

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.583

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.336

Alfa AF: 0.255 Hom.: 6108

Bravo AF: 0.415

Asia WGS AF: 0.408 AC: 1418 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	15
DANN	Benign	0.84

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: rs1807198; hg19: chr15-96878294;