dbSNP rs551936462: NR2F2:p.Pro43Pro (chr15-96332234-C-G) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_021005.4(NR2F2):c.129C>G(p.Pro43Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000634 in 1,534,484 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00067 ( 1 hom. )

Consequence

NR2F2
NM_021005.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.391

Publications

0 publications found

Variant links:

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 links:

NR2F2-AS1 (HGNC:44222): (NR2F2 antisense RNA 1)

NR2F2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 15-96332234-C-G is Benign according to our data. Variant chr15-96332234-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 241369.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.391 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.000674 (932/1382664) while in subpopulation NFE AF = 0.000819 (880/1073886). AF 95% confidence interval is 0.000774. There are 1 homozygotes in GnomAdExome4. There are 455 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 41 AD gene.

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.129C>G	p.Pro43Pro	synonymous	Exon 1 of 3	NP_066285.1	F1D8R0
	NR2F2	NM_001145155.2		c.44-1842C>G		intron	N/A	NP_001138627.1	P24468-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NR2F2	ENST00000394166.8	TSL:1 MANE Select	c.129C>G	p.Pro43Pro	synonymous	Exon 1 of 3	ENSP00000377721.3	P24468-1
NR2F2	ENST00000421109.6	TSL:1	c.44-1842C>G		intron	N/A	ENSP00000401674.2	P24468-2
NR2F2	ENST00000961130.1		c.129C>G	p.Pro43Pro	synonymous	Exon 2 of 4	ENSP00000631189.1

Frequencies

GnomAD3 genomes

AF:

0.000270

AC:

AN:

151712

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000263

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000356

AC:

AN:

132036

AF XY:

0.000347

show subpopulations

Gnomad AFR exome

AF:

0.000163

Gnomad AMR exome

AF:

0.000456

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000712

Gnomad OTH exome

AF:

0.000252

GnomAD4 exome

AF:

0.000674

AC:

932

AN:

1382664

Hom.:

Cov.:

AF XY:

0.000667

AC XY:

455

AN XY:

681928

show subpopulations

African (AFR)

AF:

0.000128

AC:

AN:

31178

American (AMR)

AF:

0.000454

AC:

AN:

35268

Ashkenazi Jewish (ASJ)

AF:

0.0000811

AC:

AN:

24652

East Asian (EAS)

AF:

0.00

AC:

AN:

35360

South Asian (SAS)

AF:

0.00

AC:

AN:

78696

European-Finnish (FIN)

AF:

0.0000243

AC:

AN:

41104

Middle Eastern (MID)

AF:

0.000193

AC:

AN:

5194

European-Non Finnish (NFE)

AF:

0.000819

AC:

880

AN:

1073886

Other (OTH)

AF:

0.000488

AC:

AN:

57326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

122

182

243

304

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000270

AC:

AN:

151820

Hom.:

Cov.:

AF XY:

0.000364

AC XY:

AN XY:

74222

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41514

American (AMR)

AF:

0.000263

AC:

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5148

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10384

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000412

AC:

AN:

67926

Other (OTH)

AF:

0.00

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000299

Hom.:

Bravo

AF:

0.000340

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Congenital heart defects, multiple types, 4 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

8.0

(source)

DANN

Benign

0.86

PhyloP100

0.39

PromoterAI

0.010

Neutral

(source)

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over