Variant chr21-14964790-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_003489.4(NRIP1):c.3403C>T(p.Arg1135Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,608,510 control chromosomes in the GnomAD database, including 113 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0087 ( 7 hom., cov: 32)

Exomes 𝑓: 0.010 ( 106 hom. )

Consequence

NRIP1
NM_003489.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.41

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037371218).

BP6

Variant 21-14964790-G-A is Benign according to our data. Variant chr21-14964790-G-A is described in ClinVar as [Benign]. Clinvar id is 774533.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1331 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRIP1	NM_003489.4 linkuse as main transcript	c.3403C>T	p.Arg1135Cys	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.3403C>T	p.Arg1135Cys	missense_variant	4/4	2	NM_003489.4	ENSP00000327213	P1
NRIP1	ENST00000400199.5 linkuse as main transcript	c.3403C>T	p.Arg1135Cys	missense_variant	3/3	3		ENSP00000383060	P1
NRIP1	ENST00000400202.5 linkuse as main transcript	c.3403C>T	p.Arg1135Cys	missense_variant	3/3	5		ENSP00000383063	P1

Frequencies

GnomAD3 genomes

AF:

0.00876

AC:

1333

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00200

Gnomad AMI

AF:

0.0209

Gnomad AMR

AF:

0.0133

Gnomad ASJ

AF:

0.0326

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00456

Gnomad FIN

AF:

0.000849

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0127

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00922

AC:

2266

AN:

245718

Hom.:

AF XY:

0.00945

AC XY:

1256

AN XY:

132898

show subpopulations

Gnomad AFR exome

AF:

0.00156

Gnomad AMR exome

AF:

0.00874

Gnomad ASJ exome

AF:

0.0312

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00459

Gnomad FIN exome

AF:

0.00107

Gnomad NFE exome

AF:

0.0126

Gnomad OTH exome

AF:

0.0126

GnomAD4 exome

AF:

0.0104

AC:

15095

AN:

1456308

Hom.:

106

Cov.:

AF XY:

0.0103

AC XY:

7447

AN XY:

724454

show subpopulations

Gnomad4 AFR exome

AF:

0.00176

Gnomad4 AMR exome

AF:

0.00897

Gnomad4 ASJ exome

AF:

0.0326

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00483

Gnomad4 FIN exome

AF:

0.00201

Gnomad4 NFE exome

AF:

0.0112

Gnomad4 OTH exome

AF:

0.0117

GnomAD4 genome

AF:

0.00874

AC:

1331

AN:

152202

Hom.:

Cov.:

AF XY:

0.00848

AC XY:

631

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00200

Gnomad4 AMR

AF:

0.0133

Gnomad4 ASJ

AF:

0.0326

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.000849

Gnomad4 NFE

AF:

0.0126

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.0124

Hom.:

Bravo

AF:

0.00948

TwinsUK

AF:

0.0135

AC:

ALSPAC

AF:

0.00856

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.0133

AC:

114

ExAC

AF:

0.00890

AC:

1080

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 03, 2024	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	NRIP1: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.19

T;T;T

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.18

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.65

T;.;.

MetaRNN

Benign

0.0037

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

L;L;L

MutationTaster

Benign

0.97

D;D;D

PrimateAI

Benign

0.23

PROVEAN

Uncertain

-2.8

D;D;D

REVEL

Benign

0.057

Sift

Benign

0.095

T;T;T

Sift4G

Uncertain

0.039

D;D;D

Polyphen

0.0030

B;B;B

Vest4

0.082

MVP

0.14

MPC

0.024

ClinPred

0.012

GERP RS

1.7

Varity_R

0.11

gMVP

0.20

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