Genetic Variant NRBP1:c.662-129T>C (chr2-27436624-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_013392.4(NRBP1):c.662-129T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 716,204 control chromosomes in the GnomAD database, including 63,304 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.46 ( 17918 hom., cov: 31)

Exomes 𝑓: 0.39 ( 45386 hom. )

Consequence

NRBP1
NM_013392.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.08

Publications

18 publications found

Variant links:

Genes affected

NRBP1 (HGNC:7993): (nuclear receptor binding protein 1) Predicted to enable protein homodimerization activity. Involved in endoplasmic reticulum to Golgi vesicle-mediated transport. Located in endomembrane system. [provided by Alliance of Genome Resources, Apr 2022]

NRBP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013392.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NRBP1	NM_013392.4	MANE Select	c.662-129T>C	intron	N/A	NP_037524.1	Q9UHY1
NRBP1	NM_001321358.2		c.686-129T>C	intron	N/A	NP_001308287.1	F8W6G1
NRBP1	NM_001321359.2		c.686-129T>C	intron	N/A	NP_001308288.1	F8W6G1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NRBP1	ENST00000379852.8	TSL:1 MANE Select	c.662-129T>C	intron	N/A	ENSP00000369181.3	Q9UHY1
NRBP1	ENST00000379863.7	TSL:5	c.686-129T>C	intron	N/A	ENSP00000369192.3	F8W6G1
NRBP1	ENST00000857545.1		c.686-129T>C	intron	N/A	ENSP00000527604.1

Frequencies

GnomAD3 genomes

AF:

0.464

AC:

70476

AN:

151832

Hom.:

17873

Cov.:

show subpopulations

Gnomad AFR

AF:

0.667

Gnomad AMI

AF:

0.219

Gnomad AMR

AF:

0.471

Gnomad ASJ

AF:

0.334

Gnomad EAS

AF:

0.155

Gnomad SAS

AF:

0.424

Gnomad FIN

AF:

0.430

Gnomad MID

AF:

0.363

Gnomad NFE

AF:

0.383

Gnomad OTH

AF:

0.406

GnomAD4 exome

AF:

0.389

AC:

219338

AN:

564252

Hom.:

45386

Cov.:

AF XY:

0.387

AC XY:

116583

AN XY:

301472

show subpopulations

African (AFR)

AF:

0.664

AC:

10712

AN:

16130

American (AMR)

AF:

0.546

AC:

17339

AN:

31762

Ashkenazi Jewish (ASJ)

AF:

0.338

AC:

5920

AN:

17540

East Asian (EAS)

AF:

0.130

AC:

4358

AN:

33458

South Asian (SAS)

AF:

0.418

AC:

24158

AN:

57782

European-Finnish (FIN)

AF:

0.430

AC:

17972

AN:

41794

Middle Eastern (MID)

AF:

0.360

AC:

1404

AN:

3898

European-Non Finnish (NFE)

AF:

0.379

AC:

125493

AN:

331502

Other (OTH)

AF:

0.394

AC:

11982

AN:

30386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

6277

12554

18830

25107

31384

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1126

2252

3378

4504

5630

<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:

0.465

AC:

70584

AN:

151952

Hom.:

17918

Cov.:

AF XY:

0.463

AC XY:

34398

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.667

AC:

27643

AN:

41438

American (AMR)

AF:

0.472

AC:

7194

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.334

AC:

1161

AN:

3472

East Asian (EAS)

AF:

0.156

AC:

806

AN:

5172

South Asian (SAS)

AF:

0.425

AC:

2042

AN:

4806

European-Finnish (FIN)

AF:

0.430

AC:

4535

AN:

10550

Middle Eastern (MID)

AF:

0.374

AC:

110

AN:

294

European-Non Finnish (NFE)

AF:

0.383

AC:

26028

AN:

67946

Other (OTH)

AF:

0.410

AC:

866

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1817

3633

5450

7266

9083

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

620

1240

1860

2480

3100

<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:

0.436

Hom.:

2463

Bravo

AF:

0.475

Asia WGS

AF:

0.360

AC:

1251

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.33

(source)

DANN

Benign

0.42

PhyloP100

-1.1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over