15-96335208-T-C

Variant names:

• chr15-96335208-T-C
• rs2001192
• NM_021005.4:c.970+605T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021005.4(NR2F2):​c.970+605T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,240 control chromosomes in the GnomAD database, including 3,982 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 0.20 (3982 hom., cov: 33)
• Consequence: NR2F2 NM_021005.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101
• Publications: 2 publications found

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]

NR2F2-AS1 (HGNC:44222): (NR2F2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR2F2	NM_021005.4	c.970+605T>C		intron_variant	Intron 2 of 2	ENST00000394166.8	NP_066285.1
NR2F2	NM_001145155.2	c.571+605T>C		intron_variant	Intron 2 of 2		NP_001138627.1
NR2F2	NM_001145156.1	c.511+605T>C		intron_variant	Intron 2 of 2		NP_001138628.1
NR2F2	NM_001145157.2	c.511+605T>C		intron_variant	Intron 2 of 2		NP_001138629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR2F2	ENST00000394166.8	c.970+605T>C		intron_variant	Intron 2 of 2	1	NM_021005.4	ENSP00000377721.3

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31140 AN: 152122 Hom.: 3983 Cov.: 33

Gnomad AFR AF: 0.0918

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.205 AC: 31156 AN: 152240 Hom.: 3982 Cov.: 33 AF XY: 0.211 AC XY: 15685 AN XY: 74438

African (AFR) AF: 0.0919 AC: 3820 AN: 41550

American (AMR) AF: 0.282 AC: 4318 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 633 AN: 3468

East Asian (EAS) AF: 0.578 AC: 2989 AN: 5174

South Asian (SAS) AF: 0.176 AC: 852 AN: 4830

European-Finnish (FIN) AF: 0.266 AC: 2818 AN: 10600

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15174 AN: 68000

Other (OTH) AF: 0.194 AC: 410 AN: 2114

Alfa AF: 0.225 Hom.: 2587

Bravo AF: 0.206

Asia WGS AF: 0.320 AC: 1109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.57
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2001192; hg19: chr15-96878437;