15-96331144-C-T

Position:

• chr15-96331144-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_021005.4(NR2F2):​c.-962C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0434 in 1,075,652 control chromosomes in the GnomAD database, including 2,131 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.054 (358 hom., cov: 30)
  • Exomes 𝑓: 0.042 (1773 hom.)
• Consequence: NR2F2 NM_021005.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.01

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 15-96331144-C-T is Benign according to our data. Variant chr15-96331144-C-T is described in ClinVar as [Benign]. Clinvar id is 1262787.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR2F2	NM_021005.4	c.-962C>T		5_prime_UTR_variant	1/3	ENST00000394166.8	NP_066285.1
NR2F2	NM_001145155.2	c.44-2932C>T		intron_variant			NP_001138627.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR2F2	ENST00000394166.8	c.-962C>T		5_prime_UTR_variant	1/3	1	NM_021005.4	ENSP00000377721	P1
NR2F2	ENST00000421109.6	c.44-2932C>T		intron_variant		1		ENSP00000401674

Frequencies

GnomAD3 genomes AF: 0.0542 AC: 7956 AN: 146876 Hom.: 360 Cov.: 30

Gnomad AFR AF: 0.0606

Gnomad AMI AF: 0.00335

Gnomad AMR AF: 0.0402

Gnomad ASJ AF: 0.0292

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.0228

Gnomad MID AF: 0.0882

Gnomad NFE AF: 0.0353

Gnomad OTH AF: 0.0579

GnomAD4 exome AF: 0.0418 AC: 38778 AN: 928672 Hom.: 1773 Cov.: 16 AF XY: 0.0419 AC XY: 18271 AN XY: 436106

Gnomad4 AFR exome AF: 0.0595

Gnomad4 AMR exome AF: 0.0386

Gnomad4 ASJ exome AF: 0.0323

Gnomad4 EAS exome AF: 0.316

Gnomad4 SAS exome AF: 0.176

Gnomad4 FIN exome AF: 0.0284

Gnomad4 NFE exome AF: 0.0327

Gnomad4 OTH exome AF: 0.0590

GnomAD4 genome AF: 0.0541 AC: 7954 AN: 146980 Hom.: 358 Cov.: 30 AF XY: 0.0561 AC XY: 4011 AN XY: 71534

Gnomad4 AFR AF: 0.0604

Gnomad4 AMR AF: 0.0402

Gnomad4 ASJ AF: 0.0292

Gnomad4 EAS AF: 0.245

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.0228

Gnomad4 NFE AF: 0.0353

Gnomad4 OTH AF: 0.0578

Alfa AF: 0.0428 Hom.: 30

Bravo AF: 0.0532

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 20, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	18
DANN	Benign	0.91

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: rs111947874; hg19: chr15-96874373;