Variant chr21-14966851-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003489.4(NRIP1):c.1342C>G(p.Arg448Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0926 in 1,613,906 control chromosomes in the GnomAD database, including 7,528 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.070 ( 501 hom., cov: 32)

Exomes 𝑓: 0.095 ( 7027 hom. )

Consequence

NRIP1
NM_003489.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.92

Variant links:

Genes affected

NRIP1 (HGNC:8001): (nuclear receptor interacting protein 1) Nuclear receptor interacting protein 1 (NRIP1) is a nuclear protein that specifically interacts with the hormone-dependent activation domain AF2 of nuclear receptors. Also known as RIP140, this protein modulates transcriptional activity of the estrogen receptor. [provided by RefSeq, Jul 2008]

NRIP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001825124).

BP6

Variant 21-14966851-G-C is Benign according to our data. Variant chr21-14966851-G-C is described in ClinVar as [Benign]. Clinvar id is 1593778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRIP1	NM_003489.4 linkuse as main transcript	c.1342C>G	p.Arg448Gly	missense_variant	4/4	ENST00000318948.7	NP_003480.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
NRIP1	ENST00000318948.7 linkuse as main transcript	c.1342C>G	p.Arg448Gly	missense_variant	4/4	2	NM_003489.4	ENSP00000327213	P1
NRIP1	ENST00000400199.5 linkuse as main transcript	c.1342C>G	p.Arg448Gly	missense_variant	3/3	3		ENSP00000383060	P1
NRIP1	ENST00000400202.5 linkuse as main transcript	c.1342C>G	p.Arg448Gly	missense_variant	3/3	5		ENSP00000383063	P1

Frequencies

GnomAD3 genomes

AF:

0.0702

AC:

10665

AN:

152030

Hom.:

501

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0193

Gnomad AMI

AF:

0.0736

Gnomad AMR

AF:

0.0483

Gnomad ASJ

AF:

0.0971

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.0668

Gnomad FIN

AF:

0.0977

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.0733

GnomAD3 exomes

AF:

0.0793

AC:

19926

AN:

251244

Hom.:

1015

AF XY:

0.0815

AC XY:

11071

AN XY:

135788

show subpopulations

Gnomad AFR exome

AF:

0.0158

Gnomad AMR exome

AF:

0.0368

Gnomad ASJ exome

AF:

0.115

Gnomad EAS exome

AF:

0.00109

Gnomad SAS exome

AF:

0.0755

Gnomad FIN exome

AF:

0.103

Gnomad NFE exome

AF:

0.107

Gnomad OTH exome

AF:

0.0848

GnomAD4 exome

AF:

0.0949

AC:

138778

AN:

1461758

Hom.:

7027

Cov.:

AF XY:

0.0947

AC XY:

68844

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.0142

Gnomad4 AMR exome

AF:

0.0388

Gnomad4 ASJ exome

AF:

0.114

Gnomad4 EAS exome

AF:

0.000806

Gnomad4 SAS exome

AF:

0.0778

Gnomad4 FIN exome

AF:

0.106

Gnomad4 NFE exome

AF:

0.104

Gnomad4 OTH exome

AF:

0.0842

GnomAD4 genome

AF:

0.0701

AC:

10661

AN:

152148

Hom.:

501

Cov.:

AF XY:

0.0669

AC XY:

4980

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0192

Gnomad4 AMR

AF:

0.0482

Gnomad4 ASJ

AF:

0.0971

Gnomad4 EAS

AF:

0.00212

Gnomad4 SAS

AF:

0.0665

Gnomad4 FIN

AF:

0.0977

Gnomad4 NFE

AF:

0.106

Gnomad4 OTH

AF:

0.0726

Alfa

AF:

0.0958

Hom.:

581

Bravo

AF:

0.0636

TwinsUK

AF:

0.116

AC:

430

ALSPAC

AF:

0.102

AC:

393

ESP6500AA

AF:

0.0179

AC:

ESP6500EA

AF:

0.104

AC:

898

ExAC

AF:

0.0805

AC:

9769

Asia WGS

AF:

0.0340

AC:

116

AN:

3476

EpiCase

AF:

0.101

EpiControl

AF:

0.0986

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 24, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

T;T;T

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.62

T;.;.

MetaRNN

Benign

0.0018

T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.6

M;M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-6.5

D;D;D

REVEL

Benign

0.14

Sift

Uncertain

0.019

D;D;D

Sift4G

Uncertain

0.010

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.27

MPC

0.19

ClinPred

0.020

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.71

gMVP

0.35

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over