chr21-14964724-ATTCT-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_003489.4(NRIP1):c.3465_3468delAGAA(p.Lys1155AsnfsTer15) variant causes a frameshift change. The variant allele was found at a frequency of 0.000113 in 1,539,272 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

NRIP1
NM_003489.4 frameshift

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 6.24

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:

ENSG00000235609 (HGNC:):

ENSG00000235609 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 19 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRIP1	NM_003489.4 link	c.3465_3468delAGAA	p.Lys1155AsnfsTer15	frameshift_variant	Exon 4 of 4	ENST00000318948.7	NP_003480.2	P48552A8K171

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NRIP1	ENST00000318948.7 link	c.3465_3468delAGAA	p.Lys1155AsnfsTer15	frameshift_variant	Exon 4 of 4	2	NM_003489.4	ENSP00000327213.4	P48552
NRIP1	ENST00000400199.5 link	c.3465_3468delAGAA	p.Lys1155AsnfsTer15	frameshift_variant	Exon 3 of 3	3		ENSP00000383060.1	P48552
NRIP1	ENST00000400202.5 link	c.3465_3468delAGAA	p.Lys1155AsnfsTer15	frameshift_variant	Exon 3 of 3	5		ENSP00000383063.1	P48552
ENSG00000235609	ENST00000432230.6 link	n.87+49616_87+49619delAGAA		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000855

AC:

AN:

187230

AF XY:

0.0000702

show subpopulations

Gnomad AFR exome

AF:

0.0000649

Gnomad AMR exome

AF:

0.0000942

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000564

Gnomad NFE exome

AF:

0.0000548

Gnomad OTH exome

AF:

0.000233

GnomAD4 exome

AF:

0.000112

AC:

155

AN:

1387020

Hom.:

AF XY:

0.000114

AC XY:

AN XY:

684354

show subpopulations

Gnomad4 AFR exome

AF:

0.0000656

AC:

AN:

30482

Gnomad4 AMR exome

AF:

0.000101

AC:

AN:

29580

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

20932

Gnomad4 EAS exome

AF:

0.0000509

AC:

AN:

39274

Gnomad4 SAS exome

AF:

0.000153

AC:

AN:

71812

Gnomad4 FIN exome

AF:

0.0000198

AC:

AN:

50498

Gnomad4 NFE exome

AF:

0.000119

AC:

129

AN:

1081850

Gnomad4 Remaining exome

AF:

0.000122

AC:

AN:

57200

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000125

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0000963

AC:

0.0000962603

AN:

0.0000962603

Gnomad4 AMR

AF:

0.000131

AC:

0.000130856

AN:

0.000130856

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.000193

AC:

0.000192901

AN:

0.000192901

Gnomad4 SAS

AF:

0.000207

AC:

0.000206868

AN:

0.000206868

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000162

AC:

0.000161741

AN:

0.000161741

Gnomad4 OTH

AF:

0.00

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000136

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 08, 2024

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant summary: NRIP1 c.3465_3468delAGAA (p.Lys1155AsnfsX15) causes a frameshift which results in an extension of the protein, altering the last 4 amino acids in the native protein sequence and extending the protein by 10 amino acid. The molecular mechanism of disease attributed to NRIP1 is gain-of-function. The variant allele was found at a frequency of 0.00011 in 1539272 control chromosomes. To our knowledge, no occurrence of c.3465_3468delAGAA in individuals affected with Congenital Anomalies Of Kidney And Urinary Tract 3 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1723300). Based on the evidence outlined above, the variant was classified as uncertain significance. -

Congenital anomalies of kidney and urinary tract 3

Uncertain:1

Mar 22, 2023

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:research

- -

not provided

Uncertain:1

Oct 24, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is present in population databases (rs776126740, gnomAD 0.03%). This sequence change results in a frameshift in the NRIP1 gene (p.Lys1155Asnfs*15). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 4 amino acid(s) of the NRIP1 protein and extend the protein by 10 additional amino acid residues. This variant has not been reported in the literature in individuals affected with NRIP1-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=28/172

disease causing

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