18-49929610-GAAAAAAA-G

Variant names:

• chr18-49929610-GAAAAAAA-G
• rs56278513
• NM_001080467.3:c.2004-19_2004-13delTTTTTTT

Variant summary

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

The NM_001080467.3(MYO5B):​c.2004-19_2004-13delTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000865 in 1,155,606 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 8.7e-7 (0 hom.)
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06
• Publications: 0 publications found

Genes affected

MYO5B (HGNC:7603): (myosin VB) The protein encoded by this gene, together with other proteins, may be involved in plasma membrane recycling. Mutations in this gene are associated with microvillous inclusion disease. [provided by RefSeq, Sep 2009]

MYO5B Gene-Disease associations (from GenCC):

• microvillus inclusion disease

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• cholestasis, progressive familial intrahepatic, 10

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• progressive familial intrahepatic cholestasis type 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080467.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5B	NM_001080467.3	MANE Select	c.2004-19_2004-13delTTTTTTT		intron	N/A	NP_001073936.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5B	ENST00000285039.12	TSL:1 MANE Select	c.2004-19_2004-13delTTTTTTT		intron	N/A	ENSP00000285039.6
	MYO5B	ENST00000697219.1		c.1800-19_1800-13delTTTTTTT		intron	N/A	ENSP00000513188.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 8.65e-7 AC: 1 AN: 1155606 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 577646

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26604

American (AMR) AF: 0.0000312 AC: 1 AN: 32072

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22244

East Asian (EAS) AF: 0.00 AC: 0 AN: 33536

South Asian (SAS) AF: 0.00 AC: 0 AN: 70378

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36188

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3522

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 882018

Other (OTH) AF: 0.00 AC: 0 AN: 49044

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1

Splicing

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

Other links and lift over

dbSNP: rs56278513; hg19: chr18-47455980;