rs704791

Variant names:

• chr2-27434300-T-C
• rs704791
• NM_013392.4:c.436-171T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013392.4(NRBP1):​c.436-171T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 152,042 control chromosomes in the GnomAD database, including 17,914 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 (17914 hom., cov: 32)
• Consequence: NRBP1 NM_013392.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 20 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRBP1	NM_013392.4	c.436-171T>C		intron_variant	Intron 4 of 17	ENST00000379852.8	NP_037524.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRBP1	ENST00000379852.8	c.436-171T>C		intron_variant	Intron 4 of 17	1	NM_013392.4	ENSP00000369181.3

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70499 AN: 151924 Hom.: 17870 Cov.: 32

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.407

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.464 AC: 70605 AN: 152042 Hom.: 17914 Cov.: 32 AF XY: 0.463 AC XY: 34398 AN XY: 74314

African (AFR) AF: 0.667 AC: 27662 AN: 41468

American (AMR) AF: 0.472 AC: 7211 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1161 AN: 3470

East Asian (EAS) AF: 0.154 AC: 799 AN: 5190

South Asian (SAS) AF: 0.424 AC: 2042 AN: 4816

European-Finnish (FIN) AF: 0.429 AC: 4515 AN: 10530

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 26039 AN: 67974

Other (OTH) AF: 0.410 AC: 865 AN: 2108

Alfa AF: 0.403 Hom.: 6692

Bravo AF: 0.475

Asia WGS AF: 0.358 AC: 1243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.5
DANN	Benign	0.78
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs704791; hg19: chr2-27657167;