rs2288539

Variant names:

• chr19-17240726-G-A
• rs2288539
• NM_005234.4:c.318C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005234.4(NR2F6):​c.318C>T​(p.Asn106Asn) 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
• Publications: 18 publications found

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]

ENSG00000269095 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NR2F6	NM_005234.4	c.318C>T	p.Asn106Asn	synonymous_variant	Exon 2 of 4	ENST00000291442.4	NP_005225.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR2F6	ENST00000291442.4	c.318C>T	p.Asn106Asn	synonymous_variant	Exon 2 of 4	1	NM_005234.4	ENSP00000291442.2
ENSG00000269095	ENST00000594059.1	c.-43C>T		5_prime_UTR_variant	Exon 4 of 5	4		ENSP00000473056.1
NR2F6	ENST00000596878.1	c.-43C>T		5_prime_UTR_variant	Exon 2 of 3	3		ENSP00000471686.1

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

GnomAD2 exomes AF: 0.170 AC: 42628 AN: 251344 AF XY: 0.163

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 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

African (AFR) AF: 0.250 AC: 8383 AN: 33474

American (AMR) AF: 0.317 AC: 14176 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0973 AC: 2542 AN: 26132

East Asian (EAS) AF: 0.215 AC: 8519 AN: 39692

South Asian (SAS) AF: 0.225 AC: 19380 AN: 86254

European-Finnish (FIN) AF: 0.0828 AC: 4421 AN: 53408

Middle Eastern (MID) AF: 0.164 AC: 947 AN: 5768

European-Non Finnish (NFE) AF: 0.110 AC: 121792 AN: 1111958

Other (OTH) AF: 0.139 AC: 8373 AN: 60390

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

African (AFR) AF: 0.249 AC: 10341 AN: 41490

American (AMR) AF: 0.220 AC: 3353 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0977 AC: 339 AN: 3470

East Asian (EAS) AF: 0.225 AC: 1168 AN: 5180

South Asian (SAS) AF: 0.225 AC: 1087 AN: 4822

European-Finnish (FIN) AF: 0.0912 AC: 968 AN: 10610

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7218 AN: 68020

Other (OTH) AF: 0.147 AC: 310 AN: 2114

Alfa AF: 0.128 Hom.: 2587

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
PhyloP100		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2288539; hg19: chr19-17351535; COSMIC: COSV52245742;