Variant chr21-14964745-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_003489.4(NRIP1):c.3448G>A(p.Val1150Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000333 in 1,560,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

NRIP1
NM_003489.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.213

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07274541).

BS2

High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRIP1	NM_003489.4 linkuse as main transcript	c.3448G>A	p.Val1150Met	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.3448G>A	p.Val1150Met	missense_variant	4/4	2	NM_003489.4	P1
NRIP1	ENST00000400199.5 linkuse as main transcript	c.3448G>A	p.Val1150Met	missense_variant	3/3	3		P1
NRIP1	ENST00000400202.5 linkuse as main transcript	c.3448G>A	p.Val1150Met	missense_variant	3/3	5		P1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000245

AC:

AN:

203762

Hom.:

AF XY:

0.0000454

AC XY:

AN XY:

110070

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000186

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000204

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000319

AC:

AN:

1408464

Hom.:

Cov.:

AF XY:

0.0000272

AC XY:

AN XY:

698186

show subpopulations

Gnomad4 AFR exome

AF:

0.0000325

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000127

Gnomad4 SAS exome

AF:

0.0000131

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000348

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152270

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

NRIP1-related disorder

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 26, 2023

The NRIP1 c.3448G>A variant is predicted to result in the amino acid substitution p.Val1150Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.017% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/21-16337066-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.60

CADD

Benign

8.6

DANN

Benign

0.93

DEOGEN2

Benign

0.16

T;T;T

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.76

T;.;.

M_CAP

Benign

0.0092

MetaRNN

Benign

0.073

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.79

N;N;N

MutationTaster

Benign

0.99

N;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-2.0

N;N;N

REVEL

Benign

0.033

Sift

Benign

0.20

T;T;T

Sift4G

Benign

0.22

T;T;T

Polyphen

0.13

B;B;B

Vest4

0.24

MutPred

0.28

Gain of disorder (P = 0.0267);Gain of disorder (P = 0.0267);Gain of disorder (P = 0.0267);

MVP

0.068

MPC

0.023

ClinPred

0.025

GERP RS

-0.29

Varity_R

0.054

gMVP

0.48

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