chr15-96332041-C-T

Position:

• chr15-96332041-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_021005.4(NR2F2):​c.-65C>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 0.0216 in 1,244,404 control chromosomes in the GnomAD database, including 4,597 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (2794 hom., cov: 31)
  • Exomes 𝑓: 0.010 (1803 hom.)
• Consequence: NR2F2 NM_021005.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.18

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 15-96332041-C-T is Benign according to our data. Variant chr15-96332041-C-T is described in ClinVar as [Benign]. Clinvar id is 1248399.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR2F2	NM_021005.4	c.-65C>T		5_prime_UTR_variant	1/3	ENST00000394166.8	NP_066285.1
NR2F2	NM_001145155.2	c.44-2035C>T		intron_variant			NP_001138627.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR2F2	ENST00000394166.8	c.-65C>T		5_prime_UTR_variant	1/3	1	NM_021005.4	ENSP00000377721	P1
NR2F2	ENST00000421109.6	c.44-2035C>T		intron_variant		1		ENSP00000401674

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15860 AN: 151578 Hom.: 2783 Cov.: 31

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0449

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0417

Gnomad NFE AF: 0.00153

Gnomad OTH AF: 0.0716

GnomAD4 exome AF: 0.0100 AC: 10952 AN: 1092720 Hom.: 1803 Cov.: 30 AF XY: 0.00920 AC XY: 4803 AN XY: 522042

Gnomad4 AFR exome AF: 0.387

Gnomad4 AMR exome AF: 0.0350

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000554

Gnomad4 FIN exome AF: 0.0000755

Gnomad4 NFE exome AF: 0.00106

Gnomad4 OTH exome AF: 0.0250

GnomAD4 genome AF: 0.105 AC: 15899 AN: 151684 Hom.: 2794 Cov.: 31 AF XY: 0.101 AC XY: 7511 AN XY: 74130

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.0448

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00153

Gnomad4 OTH AF: 0.0714

Alfa AF: 0.0952 Hom.: 195

Bravo AF: 0.120

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	20
DANN	Benign	0.96
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs142499350; hg19: chr15-96875270;