1-1615470-C-G

Variant names:

• chr1-1615470-C-G
• rs775387822
• XM_047446594.1:c.11C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The XM_047446594.1(MIB2):​c.11C>G​(p.Ala4Gly) 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. 12/18 in silico tools predict 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: 0.0000088 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MIB2 XM_047446594.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.534

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07820508).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIB2	NM_001170687.4	c.-293C>G		upstream_gene_variant		ENST00000355826.10	NP_001164158.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIB2	ENST00000355826.10	c.-293C>G		upstream_gene_variant		1	NM_001170687.4	ENSP00000348081.6

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.0000961 AC: 10 AN: 104110 Hom.: 0 AF XY: 0.0000880 AC XY: 5 AN XY: 56804

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000460

Gnomad ASJ exome AF: 0.000167

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000115

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000155

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000885 AC: 12 AN: 1356438 Hom.: 0 Cov.: 32 AF XY: 0.00000599 AC XY: 4 AN XY: 667698

Gnomad4 AFR exome AF: 0.0000343

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000431

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000135

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000749

Gnomad4 OTH exome AF: 0.0000176

GnomAD4 genome Cov.: 34

ExAC AF: 0.000225 AC: 5

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	4.9
DANN	Benign	0.90
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.32	T;T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.078	T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.050	N;N;N;N
REVEL	Benign	0.034
Sift	Pathogenic	0.0	D;D;D;D
Vest4		0.15
MVP		0.12
MPC		0.91
ClinPred		0.61	D
GERP RS		1.6
gMVP		0.036

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

LitVar

Other links and lift over

dbSNP: rs775387822; hg19: chr1-1550850; COSMIC: COSV61755439; COSMIC: COSV61755439;