Variant chr21-14964738-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.3455C>T(p.Thr1152Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000291 in 1,555,628 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 2 hom. )

Consequence

NRIP1
NM_003489.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 7.77

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=0.011401266).

BP6

Variant 21-14964738-G-A is Benign according to our data. Variant chr21-14964738-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 734220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 180 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRIP1	NM_003489.4 linkuse as main transcript	c.3455C>T	p.Thr1152Met	missense_variant	4/4	ENST00000318948.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
NRIP1	ENST00000318948.7 linkuse as main transcript	c.3455C>T	p.Thr1152Met	missense_variant	4/4	2	NM_003489.4	P1
NRIP1	ENST00000400199.5 linkuse as main transcript	c.3455C>T	p.Thr1152Met	missense_variant	3/3	3		P1
NRIP1	ENST00000400202.5 linkuse as main transcript	c.3455C>T	p.Thr1152Met	missense_variant	3/3	5		P1

Frequencies

GnomAD3 genomes

AF:

0.00118

AC:

180

AN:

151946

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00394

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000960

GnomAD3 exomes

AF:

0.000500

AC:

100

AN:

199960

Hom.:

AF XY:

0.000399

AC XY:

AN XY:

107774

show subpopulations

Gnomad AFR exome

AF:

0.00426

Gnomad AMR exome

AF:

0.000354

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000896

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000621

Gnomad OTH exome

AF:

0.000432

GnomAD4 exome

AF:

0.000195

AC:

273

AN:

1403564

Hom.:

Cov.:

AF XY:

0.000211

AC XY:

147

AN XY:

695172

show subpopulations

Gnomad4 AFR exome

AF:

0.00423

Gnomad4 AMR exome

AF:

0.000419

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.000664

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000477

Gnomad4 OTH exome

AF:

0.000381

GnomAD4 genome

AF:

0.00118

AC:

180

AN:

152064

Hom.:

Cov.:

AF XY:

0.00108

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00393

Gnomad4 AMR

AF:

0.000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000950

Alfa

AF:

0.000764

Hom.:

Bravo

AF:

0.00131

ESP6500AA

AF:

0.00431

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000478

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 18, 2024	- -

Congenital anomalies of kidney and urinary tract 3

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Johns Hopkins Genomics, Johns Hopkins University

Dec 17, 2020

- -

NRIP1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 09, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;T;T

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.88

D;.;.

M_CAP

Benign

0.0061

MetaRNN

Benign

0.011

T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.3

M;M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.6

D;D;D

REVEL

Uncertain

0.33

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0050

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.38

MVP

0.20

MPC

0.16

ClinPred

0.020

GERP RS

5.7

Varity_R

0.26

gMVP

0.61

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