2-27441752-C-G

Variant names:

• chr2-27441752-C-G
• NM_013392.4:c.1548C>G
• NRBP1 p.Asn516Lys

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013392.4(NRBP1):​c.1548C>G​(p.Asn516Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NRBP1 NM_013392.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.19
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.078350425).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRBP1	NM_013392.4	MANE Select	c.1548C>G	p.Asn516Lys	missense	Exon 18 of 18	NP_037524.1	Q9UHY1
	NRBP1	NM_001321358.2		c.1572C>G	p.Asn524Lys	missense	Exon 19 of 19	NP_001308287.1	F8W6G1
	NRBP1	NM_001321359.2		c.1572C>G	p.Asn524Lys	missense	Exon 19 of 19	NP_001308288.1	F8W6G1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRBP1	ENST00000379852.8	TSL:1 MANE Select	c.1548C>G	p.Asn516Lys	missense	Exon 18 of 18	ENSP00000369181.3	Q9UHY1
	NRBP1	ENST00000379863.7	TSL:5	c.1572C>G	p.Asn524Lys	missense	Exon 19 of 19	ENSP00000369192.3	F8W6G1
	NRBP1	ENST00000857545.1		c.1572C>G	p.Asn524Lys	missense	Exon 19 of 19	ENSP00000527604.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Uncertain	24
DANN	Benign	0.88
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.072
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		3.2
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	0.47	N
REVEL	Benign	0.10
Sift	Benign	1.0	T
Sift4G	Benign	0.94	T
Varity_R		0.22
gMVP		0.50
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-27664619;