chr15-96334870-C-T

Variant names:

• chr15-96334870-C-T
• rs1574570
• NM_021005.4:c.970+267C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_021005.4(NR2F2):​c.970+267C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,284 control chromosomes in the GnomAD database, including 5,400 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.26 (5400 hom., cov: 34)
• Consequence: NR2F2 NM_021005.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0180
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 15-96334870-C-T is Benign according to our data. Variant chr15-96334870-C-T is described in ClinVar as Benign. ClinVar VariationId is 1229872.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021005.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR2F2	NM_021005.4	MANE Select	c.970+267C>T		intron	N/A	NP_066285.1	F1D8R0
	NR2F2	NM_001145155.2		c.571+267C>T		intron	N/A	NP_001138627.1	P24468-2
	NR2F2	NM_001145156.1		c.511+267C>T		intron	N/A	NP_001138628.1	P24468-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR2F2	ENST00000394166.8	TSL:1 MANE Select	c.970+267C>T		intron	N/A	ENSP00000377721.3	P24468-1
	NR2F2	ENST00000421109.6	TSL:1	c.571+267C>T		intron	N/A	ENSP00000401674.2	P24468-2
	NR2F2	ENST00000453270.2	TSL:1	c.511+267C>T		intron	N/A	ENSP00000389853.2	P24468-3

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38834 AN: 152166 Hom.: 5397 Cov.: 34

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.231

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

GnomAD4 genome AF: 0.255 AC: 38861 AN: 152284 Hom.: 5400 Cov.: 34 AF XY: 0.260 AC XY: 19332 AN XY: 74450

African (AFR) AF: 0.266 AC: 11056 AN: 41572

American (AMR) AF: 0.306 AC: 4681 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 633 AN: 3470

East Asian (EAS) AF: 0.577 AC: 2982 AN: 5172

South Asian (SAS) AF: 0.177 AC: 855 AN: 4830

European-Finnish (FIN) AF: 0.266 AC: 2824 AN: 10608

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15195 AN: 68014

Other (OTH) AF: 0.231 AC: 487 AN: 2106

Alfa AF: 0.241 Hom.: 542

Bravo AF: 0.264

Asia WGS AF: 0.329 AC: 1140 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.5
DANN	Benign	0.86
PhyloP100		-0.018
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: rs1574570; hg19: chr15-96878099;