19-17244016-C-T

Position:

• chr19-17244016-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR2F6	NM_005234.4	c.278+927G>A		intron_variant		ENST00000291442.4	NP_005225.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR2F6	ENST00000291442.4	c.278+927G>A		intron_variant		1	NM_005234.4	ENSP00000291442.2
ENSG00000269095	ENST00000594059.1	c.-82-3251G>A		intron_variant		4		ENSP00000473056.1
NR2F6	ENST00000596878.1	c.-83+217G>A		intron_variant		3		ENSP00000471686.1

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

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.151

Alfa AF: 0.164 Hom.: 3443

Bravo AF: 0.156

Asia WGS AF: 0.0550 AC: 194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs4808611; hg19: chr19-17354825;