19-17244016-C-T

Variant names:

• chr19-17244016-C-T
• rs4808611
• NM_005234.4:c.278+927G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005234.4(NR2F6):​c.278+927G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,016 control chromosomes in the GnomAD database, including 2,232 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 (2232 hom., cov: 31)
• Consequence: NR2F6 NM_005234.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 28 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005234.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR2F6	NM_005234.4	MANE Select	c.278+927G>A		intron	N/A	NP_005225.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR2F6	ENST00000291442.4	TSL:1 MANE Select	c.278+927G>A		intron	N/A	ENSP00000291442.2	P10588
	ENSG00000269095	ENST00000594059.1	TSL:4	c.-82-3251G>A		intron	N/A	ENSP00000473056.1	M0R384
	NR2F6	ENST00000943527.1		c.278+927G>A		intron	N/A	ENSP00000613586.1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25052 AN: 151898 Hom.: 2226 Cov.: 31

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.153

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.165 AC: 25076 AN: 152016 Hom.: 2232 Cov.: 31 AF XY: 0.162 AC XY: 12057 AN XY: 74298

African (AFR) AF: 0.177 AC: 7347 AN: 41442

American (AMR) AF: 0.104 AC: 1584 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 570 AN: 3466

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5172

South Asian (SAS) AF: 0.104 AC: 503 AN: 4818

European-Finnish (FIN) AF: 0.226 AC: 2389 AN: 10572

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12254 AN: 67936

Other (OTH) AF: 0.151 AC: 319 AN: 2114

Alfa AF: 0.166 Hom.: 5830

Bravo AF: 0.156

Asia WGS AF: 0.0550 AC: 194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.67
PhyloP100		-1.0
PromoterAI		-0.0082	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4808611; hg19: chr19-17354825;