18-49929610-GAAAAAA-G

Variant names:

• chr18-49929610-GAAAAAA-G
• rs56278513
• NM_001080467.3:c.2004-18_2004-13delTTTTTT

Variant summary

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

The NM_001080467.3(MYO5B):​c.2004-18_2004-13delTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000692 in 1,155,512 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: 0.0000069 (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, 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5B	NM_001080467.3	MANE Select	c.2004-18_2004-13delTTTTTT		intron	N/A	NP_001073936.1	Q9ULV0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5B	ENST00000285039.12	TSL:1 MANE Select	c.2004-18_2004-13delTTTTTT		intron	N/A	ENSP00000285039.6	Q9ULV0-1
	MYO5B	ENST00000697219.1		c.1800-18_1800-13delTTTTTT		intron	N/A	ENSP00000513188.1	A0A8V8TM52
	MYO5B	ENST00000908785.1		c.2004-18_2004-13delTTTTTT		intron	N/A	ENSP00000578844.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000692 AC: 8 AN: 1155512 Hom.: 0 AF XY: 0.0000104 AC XY: 6 AN XY: 577592

⚠️ 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: 26602

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: 33534

South Asian (SAS) AF: 0.0000142 AC: 1 AN: 70376

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36180

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

European-Non Finnish (NFE) AF: 0.00000680 AC: 6 AN: 881942

Other (OTH) AF: 0.00 AC: 0 AN: 49040

⚠️ 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;