rs138429382

Variant names:

• chr1-1616568-C-G
• rs138429382
• NM_001170687.4:c.-69C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-1616568-C-G
• chr1-1616568-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001170687.4(MIB2):​c.-69C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000963 in 1,604,290 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0052 (10 hom., cov: 34)
  • Exomes 𝑓: 0.00052 (6 hom.)
• Consequence: MIB2 NM_001170687.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.890
• Publications: 3 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]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0026254654).
• BP6: Variant 1-1616568-C-G is Benign according to our data. Variant chr1-1616568-C-G is described in ClinVar as Benign. ClinVar VariationId is 720977.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00517 (788/152322) while in subpopulation AFR AF = 0.0178 (741/41568). AF 95% confidence interval is 0.0168. There are 10 homozygotes in GnomAd4. There are 379 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

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.-69C>G		5_prime_UTR	Exon 2 of 20	NP_001164158.3	Q96AX9-1
	MIB2	NM_080875.5		c.-111C>G		5_prime_UTR	Exon 2 of 20	NP_543151.4	E9PD12
	MIB2	NM_001170686.4		c.-111C>G		5_prime_UTR	Exon 2 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.-69C>G		5_prime_UTR	Exon 2 of 20	ENSP00000348081.6	Q96AX9-1
	MIB2	ENST00000505820.7	TSL:1	c.-111C>G		5_prime_UTR	Exon 2 of 20	ENSP00000426103.3	Q96AX9-1
	MIB2	ENST00000520777.6	TSL:1	c.-111C>G		5_prime_UTR	Exon 2 of 20	ENSP00000428660.2	Q96AX9-3

Frequencies

GnomAD3 genomes AF: 0.00516 AC: 785 AN: 152202 Hom.: 10 Cov.: 34

Gnomad AFR AF: 0.0178

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00113 AC: 261 AN: 231212 AF XY: 0.000891

Gnomad AFR exome AF: 0.0172

Gnomad AMR exome AF: 0.000662

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000968

Gnomad OTH exome AF: 0.000890

GnomAD4 exome AF: 0.000521 AC: 757 AN: 1451968 Hom.: 6 Cov.: 32 AF XY: 0.000468 AC XY: 338 AN XY: 721860

African (AFR) AF: 0.0178 AC: 588 AN: 33052

American (AMR) AF: 0.00100 AC: 44 AN: 44004

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25914

East Asian (EAS) AF: 0.00 AC: 0 AN: 39226

South Asian (SAS) AF: 0.0000471 AC: 4 AN: 84952

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51332

Middle Eastern (MID) AF: 0.00209 AC: 12 AN: 5754

European-Non Finnish (NFE) AF: 0.0000190 AC: 21 AN: 1107872

Other (OTH) AF: 0.00147 AC: 88 AN: 59862

GnomAD4 genome AF: 0.00517 AC: 788 AN: 152322 Hom.: 10 Cov.: 34 AF XY: 0.00509 AC XY: 379 AN XY: 74480

African (AFR) AF: 0.0178 AC: 741 AN: 41568

American (AMR) AF: 0.00183 AC: 28 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68024

Other (OTH) AF: 0.00473 AC: 10 AN: 2116

Alfa AF: 0.00145 Hom.: 0

Bravo AF: 0.00584

ESP6500AA AF: 0.0135 AC: 51

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00150 AC: 180

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	11
DANN	Benign	0.91
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.0026	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.89
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.015
Sift	Benign	0.20	T
Sift4G	Uncertain	0.040	D
Vest4		0.16
MVP		0.048
MPC		0.43
ClinPred		0.0029	T
GERP RS		0.56
PromoterAI		0.11	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
gMVP		0.031
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs138429382; hg19: chr1-1551948;