10-63153985-A-T

Variant names:

• chr10-63153985-A-T
• rs528659735
• NM_030759.5:c.631A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_030759.5(NRBF2):​c.631A>T​(p.Ile211Leu) 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. 16/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. I211V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NRBF2 NM_030759.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 0 publications found

Genes affected

NRBF2 (HGNC:19692): (nuclear receptor binding factor 2) Involved in autophagy. Located in cytoplasm. Colocalizes with phosphatidylinositol 3-kinase complex, class III. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.030851632).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRBF2	NM_030759.5	c.631A>T	p.Ile211Leu	missense_variant	Exon 4 of 4	ENST00000277746.11	NP_110386.2
NRBF2	NM_001282405.2	c.601A>T	p.Ile201Leu	missense_variant	Exon 3 of 3		NP_001269334.1
NRBF2	XM_047425132.1	c.499A>T	p.Ile167Leu	missense_variant	Exon 3 of 3		XP_047281088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRBF2	ENST00000277746.11	c.631A>T	p.Ile211Leu	missense_variant	Exon 4 of 4	1	NM_030759.5	ENSP00000277746.6
NRBF2	ENST00000435510.6	c.601A>T	p.Ile201Leu	missense_variant	Exon 3 of 3	2		ENSP00000397502.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.0010
DANN	Benign	0.63
DEOGEN2	Benign	0.026	.;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.49	T;T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.031	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	.;N
PhyloP100		-1.3
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.34	N;N
REVEL	Benign	0.015
Sift	Benign	0.44	T;T
Sift4G	Benign	0.64	T;T
Polyphen		0.0	.;B
Vest4		0.14
MutPred		0.38		.;Gain of ubiquitination at K208 (P = 0.0428);
MVP		0.25
MPC		0.15
ClinPred		0.028	T
GERP RS		-9.7
Varity_R		0.040
gMVP		0.078
Mutation Taster		=94/6	polymorphism

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: rs528659735; hg19: chr10-64913745;