chr15-96335208-T-C

Position:

• chr15-96335208-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.86).
• 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/exons	MANE	Protein	UniProt
NR2F2	NM_021005.4	c.970+605T>C		intron_variant		ENST00000394166.8	NP_066285.1
NR2F2	NM_001145155.2	c.571+605T>C		intron_variant			NP_001138627.1
NR2F2	NM_001145156.1	c.511+605T>C		intron_variant			NP_001138628.1
NR2F2	NM_001145157.2	c.511+605T>C		intron_variant			NP_001138629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR2F2	ENST00000394166.8	c.970+605T>C		intron_variant		1	NM_021005.4	ENSP00000377721.3
NR2F2	ENST00000421109.6	c.571+605T>C		intron_variant		1		ENSP00000401674.2
NR2F2	ENST00000453270.2	c.511+605T>C		intron_variant		1		ENSP00000389853.2
NR2F2	ENST00000394171.6	c.511+605T>C		intron_variant		2		ENSP00000377726.2

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

Gnomad4 AFR AF: 0.0919

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.578

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.194

Alfa AF: 0.220 Hom.: 1455

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

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: rs2001192; hg19: chr15-96878437;