Variant chr21-14964880-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003489.4(NRIP1):c.3313A>G(p.Lys1105Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000271 in 1,613,394 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 Benign (★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 2 hom. )

Consequence

NRIP1
NM_003489.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.43

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007871568).

BP6

Variant 21-14964880-T-C is Benign according to our data. Variant chr21-14964880-T-C is described in ClinVar as [Benign]. Clinvar id is 2765400.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 51 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRIP1	NM_003489.4 linkuse as main transcript	c.3313A>G	p.Lys1105Glu	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.3313A>G	p.Lys1105Glu	missense_variant	4/4	2	NM_003489.4	P1
NRIP1	ENST00000400199.5 linkuse as main transcript	c.3313A>G	p.Lys1105Glu	missense_variant	3/3	3		P1
NRIP1	ENST00000400202.5 linkuse as main transcript	c.3313A>G	p.Lys1105Glu	missense_variant	3/3	5		P1

Frequencies

GnomAD3 genomes

AF:

0.000335

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00693

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000655

AC:

164

AN:

250344

Hom.:

AF XY:

0.000739

AC XY:

100

AN XY:

135334

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00627

Gnomad SAS exome

AF:

0.00157

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000264

AC:

386

AN:

1461088

Hom.:

Cov.:

AF XY:

0.000319

AC XY:

232

AN XY:

726880

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00471

Gnomad4 SAS exome

AF:

0.00193

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000514

GnomAD4 genome

AF:

0.000335

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.000456

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00695

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000343

Hom.:

Bravo

AF:

0.000382

ExAC

AF:

0.000749

AC:

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 04, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

T;T;T

Eigen

Benign

0.099

Eigen_PC

Benign

0.085

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.75

T;.;.

M_CAP

Benign

0.019

MetaRNN

Benign

0.0079

T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.5

M;M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-3.4

D;D;D

REVEL

Benign

0.19

Sift

Uncertain

0.0040

D;D;D

Sift4G

Uncertain

0.012

D;D;D

Polyphen

0.91

P;P;P

Vest4

0.65

MVP

0.46

MPC

0.051

ClinPred

0.15

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.58

gMVP

0.73

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