15-96334870-C-T

Position:

• chr15-96334870-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR2F2	NM_021005.4	c.970+267C>T		intron_variant		ENST00000394166.8	NP_066285.1
NR2F2	NM_001145155.2	c.571+267C>T		intron_variant			NP_001138627.1
NR2F2	NM_001145156.1	c.511+267C>T		intron_variant			NP_001138628.1
NR2F2	NM_001145157.2	c.511+267C>T		intron_variant			NP_001138629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR2F2	ENST00000394166.8	c.970+267C>T		intron_variant		1	NM_021005.4	ENSP00000377721.3
NR2F2	ENST00000421109.6	c.571+267C>T		intron_variant		1		ENSP00000401674.2
NR2F2	ENST00000453270.2	c.511+267C>T		intron_variant		1		ENSP00000389853.2
NR2F2	ENST00000394171.6	c.511+267C>T		intron_variant		2		ENSP00000377726.2

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

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.577

Gnomad4 SAS AF: 0.177

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.231

Alfa AF: 0.241 Hom.: 542

Bravo AF: 0.264

Asia WGS AF: 0.329 AC: 1140 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.5
DANN	Benign	0.86

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: rs1574570; hg19: chr15-96878099;