rs1643515691

Variant names:

• chr1-1615514-A-C
• NM_001170687.4:c.-249A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-1615514-A-C
• chr1-1615514-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001170687.4(MIB2):​c.-249A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000653 in 1,377,562 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: 0.0000065 (0 hom.)
• Consequence: MIB2 NM_001170687.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.783

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05613193).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIB2	NM_001170687.4	c.-249A>C		5_prime_UTR_variant	Exon 1 of 20	ENST00000355826.10	NP_001164158.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIB2	ENST00000355826	c.-249A>C		5_prime_UTR_variant	Exon 1 of 20	1	NM_001170687.4	ENSP00000348081.6

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000653 AC: 9 AN: 1377562 Hom.: 0 Cov.: 32 AF XY: 0.00000294 AC XY: 2 AN XY: 679930

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000286

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000743

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	6.1
DANN	Benign	0.37
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.31	T;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.056	T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.010	N;N;N;N
REVEL	Benign	0.015
Sift	Benign	0.29	T;T;T;T
Sift4G	Benign	0.23	T;T;T;T
Vest4		0.046
MutPred		0.16		Loss of phosphorylation at T19 (P = 0.0107);Loss of phosphorylation at T19 (P = 0.0107);Loss of phosphorylation at T19 (P = 0.0107);Loss of phosphorylation at T19 (P = 0.0107);
MVP		0.088
MPC		0.73
ClinPred		0.11	T
GERP RS		-0.42
gMVP		0.042

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-1550894;