1-184795698-G-A

Variant names:

• chr1-184795698-G-A
• rs141082620
• NM_052966.4:c.2066C>T

Variant summary

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

The NM_052966.4(NIBAN1):​c.2066C>T​(p.Thr689Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. T689N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: NIBAN1 NM_052966.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.248

Genes affected

NIBAN1 (HGNC:16784): (niban apoptosis regulator 1) This gene encodes a member of the family with sequence similarity 129 protein family. This gene is highly expressed in several cancer cells and may serve as a prognostic marker for certain cancers. The encoded protein may play a role in regulating p53-mediated apoptosis. [provided by RefSeq, Sep 2016]

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=0.06432533).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIBAN1	NM_052966.4	c.2066C>T	p.Thr689Ile	missense_variant	Exon 14 of 14	ENST00000367511.4	NP_443198.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NIBAN1	ENST00000367511.4	c.2066C>T	p.Thr689Ile	missense_variant	Exon 14 of 14	1	NM_052966.4	ENSP00000356481.3
NIBAN1	ENST00000417056.5	c.259+2381C>T		intron_variant	Intron 3 of 3	3		ENSP00000414039.1
NIBAN1	ENST00000487074.5	n.1538C>T		non_coding_transcript_exon_variant	Exon 9 of 9	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461734 Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4 AN XY: 727178

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111922

Other (OTH) AF: 0.0000166 AC: 1 AN: 60386

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.0
DANN	Benign	0.55
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.25
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.068
Sift	Benign	0.24	T
Sift4G	Benign	0.31	T
Polyphen		0.0020	B
Vest4		0.031
MutPred		0.33		Loss of phosphorylation at T689 (P = 0.0073);
MVP		0.11
MPC		0.078
ClinPred		0.072	T
GERP RS		3.5
Varity_R		0.024
gMVP		0.096
Mutation Taster		=99/1	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

Publications

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Other links and lift over

dbSNP: rs141082620; hg19: chr1-184764832;