2-27429286-G-T

Variant names:

• chr2-27429286-G-T
• rs780100
• NM_013392.4:c.-21+555G>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRBP1	NM_013392.4	c.-21+555G>T		intron_variant	Intron 1 of 17	ENST00000379852.8	NP_037524.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRBP1	ENST00000379852.8	c.-21+555G>T		intron_variant	Intron 1 of 17	1	NM_013392.4	ENSP00000369181.3

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69835 AN: 152010 Hom.: 17497 Cov.: 33

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: 54 AN: 208 Hom.: 10 Cov.: 0 AF XY: 0.259 AC XY: 41 AN XY: 158

Gnomad4 AFR exome AF: 0.750

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.255

Gnomad4 OTH exome AF: 0.375

GnomAD4 genome AF: 0.460 AC: 69937 AN: 152128 Hom.: 17539 Cov.: 33 AF XY: 0.459 AC XY: 34102 AN XY: 74368

Gnomad4 AFR AF: 0.657

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.407

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.4
DANN	Benign	0.87

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

Other links and lift over

dbSNP: rs780100; hg19: chr2-27652153;