Genetic Variant NM_003489.4:c.225G>A (chr21-14967968-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003489.4(NRIP1):c.225G>A(p.Gly75Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 1,613,378 control chromosomes in the GnomAD database, including 176,315 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 23322 hom., cov: 32)

Exomes 𝑓: 0.45 ( 152993 hom. )

Consequence

NRIP1
NM_003489.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.974

Publications

46 publications found

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:

ASMER1 (HGNC:53135): (adipocyte associated metabolic related lncRNA 1)

ASMER1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 21-14967968-C-T is Benign according to our data. Variant chr21-14967968-C-T is described in ClinVar as Benign. ClinVar VariationId is 1326992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.974 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRIP1	NM_003489.4 link	c.225G>A	p.Gly75Gly	synonymous_variant	Exon 4 of 4	ENST00000318948.7	NP_003480.2	P48552A8K171

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRIP1	ENST00000318948.7 link	c.225G>A	p.Gly75Gly	synonymous_variant	Exon 4 of 4	2	NM_003489.4	ENSP00000327213.4		P48552

Frequencies

GnomAD3 genomes

AF:

0.535

AC:

81200

AN:

151870

Hom.:

23296

Cov.:

show subpopulations

Gnomad AFR

AF:

0.731

Gnomad AMI

AF:

0.323

Gnomad AMR

AF:

0.559

Gnomad ASJ

AF:

0.430

Gnomad EAS

AF:

0.786

Gnomad SAS

AF:

0.438

Gnomad FIN

AF:

0.433

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.422

Gnomad OTH

AF:

0.520

GnomAD2 exomes

AF:

0.502

AC:

125512

AN:

249950

AF XY:

0.489

show subpopulations

Gnomad AFR exome

AF:

0.739

Gnomad AMR exome

AF:

0.605

Gnomad ASJ exome

AF:

0.430

Gnomad EAS exome

AF:

0.797

Gnomad FIN exome

AF:

0.438

Gnomad NFE exome

AF:

0.425

Gnomad OTH exome

AF:

0.463

GnomAD4 exome

AF:

0.450

AC:

656994

AN:

1461392

Hom.:

152993

Cov.:

AF XY:

0.448

AC XY:

325433

AN XY:

726962

show subpopulations

African (AFR)

AF:

0.740

AC:

24765

AN:

33476

American (AMR)

AF:

0.598

AC:

26684

AN:

44650

Ashkenazi Jewish (ASJ)

AF:

0.424

AC:

11080

AN:

26124

East Asian (EAS)

AF:

0.800

AC:

31752

AN:

39670

South Asian (SAS)

AF:

0.448

AC:

38658

AN:

86236

European-Finnish (FIN)

AF:

0.441

AC:

23526

AN:

53386

Middle Eastern (MID)

AF:

0.434

AC:

2501

AN:

5764

European-Non Finnish (NFE)

AF:

0.423

AC:

470277

AN:

1111710

Other (OTH)

AF:

0.460

AC:

27751

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

20417

40834

61252

81669

102086

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14656

29312

43968

58624

73280

<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:

0.535

AC:

81280

AN:

151986

Hom.:

23322

Cov.:

AF XY:

0.537

AC XY:

39867

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.731

AC:

30303

AN:

41478

American (AMR)

AF:

0.560

AC:

8544

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.430

AC:

1494

AN:

3472

East Asian (EAS)

AF:

0.787

AC:

4065

AN:

5168

South Asian (SAS)

AF:

0.437

AC:

2104

AN:

4812

European-Finnish (FIN)

AF:

0.433

AC:

4564

AN:

10540

Middle Eastern (MID)

AF:

0.469

AC:

137

AN:

292

European-Non Finnish (NFE)

AF:

0.422

AC:

28668

AN:

67938

Other (OTH)

AF:

0.525

AC:

1107

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1840

3681

5521

7362

9202

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

690

1380

2070

2760

3450

<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:

0.462

Hom.:

55879

Bravo

AF:

0.559

Asia WGS

AF:

0.608

AC:

2113

AN:

3478

EpiCase

AF:

0.426

EpiControl

AF:

0.422

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital anomalies of kidney and urinary tract 3

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

5.1

(source)

DANN

Benign

0.78

PhyloP100

0.97

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over