rs2288539

Positions:

• chr19-17240726-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005234.4(NR2F6):​c.318C>T​(p.Asn106=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,613,984 control chromosomes in the GnomAD database, including 17,082 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.16 (2445 hom., cov: 33)
  • Exomes 𝑓: 0.13 (14637 hom.)
• Consequence: NR2F6 NM_005234.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.30

Genes affected

NR2F6 (HGNC:7977): (nuclear receptor subfamily 2 group F member 6) Enables DNA-binding transcription factor activity and sequence-specific double-stranded DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=3.3 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR2F6	NM_005234.4	c.318C>T	p.Asn106=	synonymous_variant	2/4	ENST00000291442.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR2F6	ENST00000291442.4	c.318C>T	p.Asn106=	synonymous_variant	2/4	1	NM_005234.4	P1
NR2F6	ENST00000596878.1	c.-43C>T		5_prime_UTR_variant	2/3	3

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24846 AN: 152068 Hom.: 2438 Cov.: 33

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.0977

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.0912

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.147

GnomAD3 exomes AF: 0.170 AC: 42628 AN: 251344 Hom.: 4833 AF XY: 0.163 AC XY: 22102 AN XY: 135848

Gnomad AFR exome AF: 0.255

Gnomad AMR exome AF: 0.334

Gnomad ASJ exome AF: 0.105

Gnomad EAS exome AF: 0.232

Gnomad SAS exome AF: 0.225

Gnomad FIN exome AF: 0.0854

Gnomad NFE exome AF: 0.106

Gnomad OTH exome AF: 0.137

GnomAD4 exome AF: 0.129 AC: 188533 AN: 1461798 Hom.: 14637 Cov.: 32 AF XY: 0.131 AC XY: 95024 AN XY: 727212

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.317

Gnomad4 ASJ exome AF: 0.0973

Gnomad4 EAS exome AF: 0.215

Gnomad4 SAS exome AF: 0.225

Gnomad4 FIN exome AF: 0.0828

Gnomad4 NFE exome AF: 0.110

Gnomad4 OTH exome AF: 0.139

GnomAD4 genome AF: 0.163 AC: 24878 AN: 152186 Hom.: 2445 Cov.: 33 AF XY: 0.165 AC XY: 12286 AN XY: 74404

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.0977

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.0912

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.147

Alfa AF: 0.123 Hom.: 1905

Bravo AF: 0.180

Asia WGS AF: 0.227 AC: 790 AN: 3478

EpiCase AF: 0.114

EpiControl AF: 0.115

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	9.7
DANN	Benign	0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2288539; hg19: chr19-17351535; COSMIC: COSV52245742;