chr18-21741628-C-G

Variant names:

• chr18-21741628-C-G
• NM_020774.4:c.45C>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_020774.4(MIB1):​c.45C>G​(p.Gly15Gly) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MIB1 NM_020774.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.341
• Publications: 0 publications found

Genes affected

MIB1 (HGNC:21086): (MIB E3 ubiquitin protein ligase 1) This gene encodes a protein containing multiple ankyrin repeats and RING finger domains that functions as an E3 ubiquitin ligase. The encoded protein positively regulates Notch signaling by ubiquitinating the Notch receptors, thereby facilitating their endocytosis. This protein may also promote the ubiquitination and degradation of death-associated protein kinase 1 (DAPK1). [provided by RefSeq, Jun 2013]

MIB1 Gene-Disease associations (from GenCC):

• left ventricular noncompaction

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• dilated cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: G2P
• left ventricular noncompaction 7

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• isolated cleft palate

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 18-21741628-C-G is Benign according to our data. Variant chr18-21741628-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3395788.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.341 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020774.4. 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
	MIB1	NM_020774.4	MANE Select	c.45C>G	p.Gly15Gly	synonymous	Exon 1 of 21	NP_065825.1	Q86YT6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIB1	ENST00000261537.7	TSL:1 MANE Select	c.45C>G	p.Gly15Gly	synonymous	Exon 1 of 21	ENSP00000261537.6	Q86YT6
	MIB1	ENST00000955830.1		c.45C>G	p.Gly15Gly	synonymous	Exon 1 of 22	ENSP00000625889.1
	MIB1	ENST00000864012.1		c.45C>G	p.Gly15Gly	synonymous	Exon 1 of 20	ENSP00000534071.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1454316 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 723108

African (AFR) AF: 0.00 AC: 0 AN: 33034

American (AMR) AF: 0.00 AC: 0 AN: 43976

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25838

East Asian (EAS) AF: 0.00 AC: 0 AN: 38954

South Asian (SAS) AF: 0.00 AC: 0 AN: 85310

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52000

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5666

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109494

Other (OTH) AF: 0.00 AC: 0 AN: 60044

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	10
DANN	Benign	0.89
PhyloP100		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr18-19321589;