1-1615512-C-A

Variant names:

• chr1-1615512-C-A
• rs1443877600
• NM_001170687.4:c.-251C>A

Variant summary

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

The NM_001170687.4(MIB2):​c.-251C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,377,712 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: MIB2 NM_001170687.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 0 publications found

Genes affected

MIB2 (HGNC:30577): (MIB E3 ubiquitin protein ligase 2) The protein encoded by this gene is an E3 ubiquitin protein ligase that mediates ubiquitination of proteins in the Notch signaling pathway. The encoded protein may be a suppressor of melanoma invasion. [provided by RefSeq, Mar 2017]

ENSG00000272106 (HGNC:):

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=0.079761356).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001170687.4. 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
	MIB2	NM_001170687.4	MANE Select	c.-251C>A		5_prime_UTR	Exon 1 of 20	NP_001164158.3	Q96AX9-1
	MIB2	NM_080875.5		c.-293C>A		5_prime_UTR	Exon 1 of 20	NP_543151.4	E9PD12
	MIB2	NM_001170686.4		c.-293C>A		5_prime_UTR	Exon 1 of 20	NP_001164157.3	Q96AX9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIB2	ENST00000355826.10	TSL:1 MANE Select	c.-251C>A		5_prime_UTR	Exon 1 of 20	ENSP00000348081.6	Q96AX9-1
	MIB2	ENST00000505820.7	TSL:1	c.-293C>A		5_prime_UTR	Exon 1 of 20	ENSP00000426103.3	Q96AX9-1
	MIB2	ENST00000520777.6	TSL:1	c.-293C>A		5_prime_UTR	Exon 1 of 20	ENSP00000428660.2	Q96AX9-3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1377712 Hom.: 0 Cov.: 32 AF XY: 0.00000147 AC XY: 1 AN XY: 680012

African (AFR) AF: 0.00 AC: 0 AN: 30246

American (AMR) AF: 0.00 AC: 0 AN: 35366

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24926

East Asian (EAS) AF: 0.00 AC: 0 AN: 35002

South Asian (SAS) AF: 0.00 AC: 0 AN: 78232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4888

European-Non Finnish (NFE) AF: 9.29e-7 AC: 1 AN: 1076854

Other (OTH) AF: 0.0000174 AC: 1 AN: 57584

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	4.2
DANN	Benign	0.94
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.2
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.048
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Vest4		0.099
MutPred		0.17		Gain of catalytic residue at P18 (P = 0.0487)
MVP		0.13
MPC		0.51
ClinPred		0.18	T
GERP RS		1.5
PromoterAI		0.16	Neutral
gMVP		0.098
Mutation Taster		=288/12	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: rs1443877600; hg19: chr1-1550892;