chr15-96331144-C-T

Variant names:

• chr15-96331144-C-T
• rs111947874
• NM_021005.4:c.-962C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_021005.4(NR2F2):​c.-962C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0434 in 1,075,652 control chromosomes in the GnomAD database, including 2,131 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.054 (358 hom., cov: 30)
  • Exomes 𝑓: 0.042 (1773 hom.)
• Consequence: NR2F2 NM_021005.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.01
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 15-96331144-C-T is Benign according to our data. Variant chr15-96331144-C-T is described in ClinVar as Benign. ClinVar VariationId is 1262787.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021005.4. 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
	NR2F2	NM_021005.4	MANE Select	c.-962C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	NP_066285.1	F1D8R0
	NR2F2	NM_021005.4	MANE Select	c.-962C>T		5_prime_UTR	Exon 1 of 3	NP_066285.1	F1D8R0
	NR2F2	NM_001145155.2		c.44-2932C>T		intron	N/A	NP_001138627.1	P24468-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR2F2	ENST00000394166.8	TSL:1 MANE Select	c.-962C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000377721.3	P24468-1
	NR2F2	ENST00000394166.8	TSL:1 MANE Select	c.-962C>T		5_prime_UTR	Exon 1 of 3	ENSP00000377721.3	P24468-1
	NR2F2	ENST00000421109.6	TSL:1	c.44-2932C>T		intron	N/A	ENSP00000401674.2	P24468-2

Frequencies

GnomAD3 genomes AF: 0.0542 AC: 7956 AN: 146876 Hom.: 360 Cov.: 30

Gnomad AFR AF: 0.0606

Gnomad AMI AF: 0.00335

Gnomad AMR AF: 0.0402

Gnomad ASJ AF: 0.0292

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.0228

Gnomad MID AF: 0.0882

Gnomad NFE AF: 0.0353

Gnomad OTH AF: 0.0579

GnomAD4 exome AF: 0.0418 AC: 38778 AN: 928672 Hom.: 1773 Cov.: 16 AF XY: 0.0419 AC XY: 18271 AN XY: 436106

African (AFR) AF: 0.0595 AC: 1082 AN: 18180

American (AMR) AF: 0.0386 AC: 160 AN: 4146

Ashkenazi Jewish (ASJ) AF: 0.0323 AC: 284 AN: 8792

East Asian (EAS) AF: 0.316 AC: 4936 AN: 15628

South Asian (SAS) AF: 0.176 AC: 3151 AN: 17920

European-Finnish (FIN) AF: 0.0284 AC: 330 AN: 11614

Middle Eastern (MID) AF: 0.0787 AC: 172 AN: 2186

European-Non Finnish (NFE) AF: 0.0327 AC: 26669 AN: 816418

Other (OTH) AF: 0.0590 AC: 1994 AN: 33788

GnomAD4 genome AF: 0.0541 AC: 7954 AN: 146980 Hom.: 358 Cov.: 30 AF XY: 0.0561 AC XY: 4011 AN XY: 71534

African (AFR) AF: 0.0604 AC: 2468 AN: 40828

American (AMR) AF: 0.0402 AC: 595 AN: 14814

Ashkenazi Jewish (ASJ) AF: 0.0292 AC: 99 AN: 3394

East Asian (EAS) AF: 0.245 AC: 1228 AN: 5012

South Asian (SAS) AF: 0.186 AC: 883 AN: 4756

European-Finnish (FIN) AF: 0.0228 AC: 200 AN: 8770

Middle Eastern (MID) AF: 0.0909 AC: 26 AN: 286

European-Non Finnish (NFE) AF: 0.0353 AC: 2334 AN: 66182

Other (OTH) AF: 0.0578 AC: 118 AN: 2042

Alfa AF: 0.0428 Hom.: 30

Bravo AF: 0.0532

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	18
DANN	Benign	0.91
PhyloP100		1.0
PromoterAI		0.084	Neutral
Mutation Taster		=300/0	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: rs111947874; hg19: chr15-96874373;