Genetic Variant NRBP1:c.-21+555G>T (chr2-27429286-G-T) – 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.-21+555G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 152,336 control chromosomes in the GnomAD database, including 17,549 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 ( 17539 hom., cov: 33)

Exomes 𝑓: 0.26 ( 10 hom. )

Consequence

NRBP1
NM_013392.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0390

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=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.65 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.-21+555G>T	intron	N/A	NP_037524.1	Q9UHY1
NRBP1	NM_001321358.2		c.-26+555G>T	intron	N/A	NP_001308287.1	F8W6G1
NRBP1	NM_001321359.2		c.-21+555G>T	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.-21+555G>T	intron	N/A	ENSP00000369181.3	Q9UHY1
NRBP1	ENST00000419281.6	TSL:3	c.-106G>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000403916.2	C9JHZ6
NRBP1	ENST00000419281.6	TSL:3	c.-106G>T	5_prime_UTR	Exon 1 of 5	ENSP00000403916.2	C9JHZ6

Frequencies

GnomAD3 genomes

AF:

0.459

AC:

69835

AN:

152010

Hom.:

17497

Cov.:

show subpopulations

Gnomad AFR

AF:

0.657

Gnomad AMI

AF:

0.204

Gnomad AMR

AF:

0.469

Gnomad ASJ

AF:

0.335

Gnomad EAS

AF:

0.153

Gnomad SAS

AF:

0.424

Gnomad FIN

AF:

0.430

Gnomad MID

AF:

0.369

Gnomad NFE

AF:

0.379

Gnomad OTH

AF:

0.403

GnomAD4 exome

AF:

0.260

AC:

AN:

208

Hom.:

Cov.:

AF XY:

0.259

AC XY:

AN XY:

158

show subpopulations

African (AFR)

AF:

0.750

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.255

AC:

AN:

188

Other (OTH)

AF:

0.375

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.460

AC:

69937

AN:

152128

Hom.:

17539

Cov.:

AF XY:

0.459

AC XY:

34102

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.657

AC:

27261

AN:

41500

American (AMR)

AF:

0.470

AC:

7183

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.335

AC:

1161

AN:

3470

East Asian (EAS)

AF:

0.153

AC:

790

AN:

5154

South Asian (SAS)

AF:

0.425

AC:

2048

AN:

4824

European-Finnish (FIN)

AF:

0.430

AC:

4554

AN:

10598

Middle Eastern (MID)

AF:

0.377

AC:

110

AN:

292

European-Non Finnish (NFE)

AF:

0.379

AC:

25785

AN:

67968

Other (OTH)

AF:

0.407

AC:

859

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1873

3747

5620

7494

9367

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

616

1232

1848

2464

3080

<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:

0.335

Hom.:

1579

Bravo

AF:

0.470

Asia WGS

AF:

0.355

AC:

1235

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

9.4

(source)

DANN

Benign

0.87

PhyloP100

-0.039

PromoterAI

0.0049

Neutral

(source)

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over