Genetic Variant NR2C1:p.Asp325Asn (chr12-95049226-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_003297.4(NR2C1):c.973G>A(p.Asp325Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000317 in 1,613,650 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00030 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 1 hom. )

Consequence

NR2C1
NM_003297.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.17

Publications

5 publications found

Variant links:

Genes affected

NR2C1 (HGNC:7971): (nuclear receptor subfamily 2 group C member 1) This gene encodes a nuclear hormone receptor characterized by a highly conserved DNA binding domain (DBD), a variable hinge region, and a carboxy-terminal ligand binding domain (LBD) that is typical for all members of the steroid/thyroid hormone receptor superfamily. This protein also belongs to a large family of ligand-inducible transcription factors that regulate gene expression by binding to specific DNA sequences within promoters of target genes. Multiple alternatively spliced transcript variants have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2008]

NR2C1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0769586).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003297.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NR2C1	NM_003297.4	MANE Select	c.973G>A	p.Asp325Asn	missense	Exon 9 of 14	NP_003288.2	P13056-1
NR2C1	NM_001127362.2		c.973G>A	p.Asp325Asn	missense	Exon 9 of 12	NP_001120834.1	P13056-3
NR2C1	NM_001032287.3		c.973G>A	p.Asp325Asn	missense	Exon 9 of 12	NP_001027458.1	H9NIM3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NR2C1	ENST00000333003.10	TSL:2 MANE Select	c.973G>A	p.Asp325Asn	missense	Exon 9 of 14	ENSP00000333275.4	P13056-1
NR2C1	ENST00000393101.7	TSL:1	c.973G>A	p.Asp325Asn	missense	Exon 9 of 12	ENSP00000376813.3	P13056-2
NR2C1	ENST00000545833.5	TSL:1	n.973G>A		non_coding_transcript_exon	Exon 8 of 10

Frequencies

GnomAD3 genomes

AF:

0.000302

AC:

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.000399

AC:

100

AN:

250930

AF XY:

0.000376

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000581

Gnomad ASJ exome

AF:

0.00398

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000458

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000319

AC:

466

AN:

1461442

Hom.:

Cov.:

AF XY:

0.000337

AC XY:

245

AN XY:

727014

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33466

American (AMR)

AF:

0.0000896

AC:

AN:

44666

Ashkenazi Jewish (ASJ)

AF:

0.00348

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.000337

AC:

AN:

86150

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53378

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000277

AC:

308

AN:

1111830

Other (OTH)

AF:

0.000530

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

114

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000302

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41528

American (AMR)

AF:

0.000196

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00375

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000338

AC:

AN:

68016

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

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:

0.000515

Hom.:

Bravo

AF:

0.000340

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000428

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.000948

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.53

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

1.0

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.077

MetaSVM

Pathogenic

0.80

MutationAssessor

Uncertain

2.8

PhyloP100

6.2

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-2.9

REVEL

Uncertain

0.55

Sift

Benign

0.098

Sift4G

Benign

0.070

Polyphen

1.0

Vest4

0.63

MVP

0.74

MPC

0.18

ClinPred

0.13

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.36

gMVP

0.58

Mutation Taster

=58/42

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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