chr15-96326466-G-T

Position:

• chr15-96326466-G-T

Variant summary

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

The ENST00000421109.6(NR2F2):​c.43+114G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00857 in 845,196 control chromosomes in the GnomAD database, including 303 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (202 hom., cov: 32)
  • Exomes 𝑓: 0.0039 (101 hom.)
• Consequence: NR2F2 ENST00000421109.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.44

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 15-96326466-G-T is Benign according to our data. Variant chr15-96326466-G-T is described in ClinVar as [Benign]. Clinvar id is 1291706.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR2F2-AS1	NR_125738.1	n.163+490C>A		intron_variant, non_coding_transcript_variant
NR2F2	NM_001145155.2	c.43+114G>T		intron_variant			NP_001138627.1
NR2F2-AS1	NR_102743.1	n.163+733C>A		intron_variant, non_coding_transcript_variant
NR2F2-AS1	NR_102744.1	n.163+733C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR2F2-AS1	ENST00000560800.5	n.66+490C>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0300 AC: 4530 AN: 150980 Hom.: 200 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0116

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000840

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0221

GnomAD4 exome AF: 0.00390 AC: 2706 AN: 694102 Hom.: 101 AF XY: 0.00322 AC XY: 1185 AN XY: 367582

Gnomad4 AFR exome AF: 0.108

Gnomad4 AMR exome AF: 0.00766

Gnomad4 ASJ exome AF: 0.000265

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000398

Gnomad4 FIN exome AF: 0.0000241

Gnomad4 NFE exome AF: 0.000322

Gnomad4 OTH exome AF: 0.00849

GnomAD4 genome AF: 0.0300 AC: 4535 AN: 151094 Hom.: 202 Cov.: 32 AF XY: 0.0287 AC XY: 2114 AN XY: 73764

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.0115

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000630

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.0218

Alfa AF: 0.0239 Hom.: 18

Bravo AF: 0.0348

Asia WGS AF: 0.00693 AC: 25 AN: 3478

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	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Benign	0.91

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs73471280; hg19: chr15-96869695;