chr18-21741527-C-CCGGCGGCAG

Variant names:

• chr18-21741527-C-CCGGCGGCAG
• rs1313310854
• NM_020774.4:c.-49_-41dupAGCGGCGGC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_020774.4(MIB1):​c.-49_-41dupAGCGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000179 in 1,120,446 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: MIB1 NM_020774.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.76
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 18-21741527-C-CCGGCGGCAG is Benign according to our data. Variant chr18-21741527-C-CCGGCGGCAG is described in ClinVar as Likely_benign. ClinVar VariationId is 517912.Status of the report is criteria_provided_single_submitter, 1 stars.

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.-49_-41dupAGCGGCGGC		5_prime_UTR	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.-49_-41dupAGCGGCGGC		5_prime_UTR	Exon 1 of 21	ENSP00000261537.6	Q86YT6
	MIB1	ENST00000955830.1		c.-49_-41dupAGCGGCGGC		5_prime_UTR	Exon 1 of 22	ENSP00000625889.1
	MIB1	ENST00000864012.1		c.-49_-41dupAGCGGCGGC		5_prime_UTR	Exon 1 of 20	ENSP00000534071.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000179 AC: 2 AN: 1120446 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 541918

African (AFR) AF: 0.00 AC: 0 AN: 21886

American (AMR) AF: 0.00 AC: 0 AN: 7960

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14000

East Asian (EAS) AF: 0.00 AC: 0 AN: 25308

South Asian (SAS) AF: 0.00 AC: 0 AN: 35146

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36720

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3066

European-Non Finnish (NFE) AF: 0.00000215 AC: 2 AN: 931806

Other (OTH) AF: 0.00 AC: 0 AN: 44554

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1313310854; hg19: chr18-19321488;