18-49929610-GAAAAAAA-GAAAAAAAAAAAAAAAAAAAAAAAAA

Variant names:

• chr18-49929610-G-GAAAAAAAAAAAAAAAAAA
• rs56278513
• NM_001080467.3:c.2004-13_2004-12insTTTTTTTTTTTTTTTTTT

Variant summary

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

The NM_001080467.3(MYO5B):​c.2004-13_2004-12insTTTTTTTTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000017 (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 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5B	NM_001080467.3	c.2004-13_2004-12insTTTTTTTTTTTTTTTTTT		intron_variant	Intron 16 of 39	ENST00000285039.12	NP_001073936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO5B	ENST00000285039.12	c.2004-13_2004-12insTTTTTTTTTTTTTTTTTT		intron_variant	Intron 16 of 39	1	NM_001080467.3	ENSP00000285039.6
MYO5B	ENST00000697219.1	c.1800-13_1800-12insTTTTTTTTTTTTTTTTTT		intron_variant	Intron 14 of 37			ENSP00000513188.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000173 AC: 2 AN: 1155620 Hom.: 0 Cov.: 0 AF XY: 0.00000346 AC XY: 2 AN XY: 577652

⚠️ 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: 0.0000624 AC: 2 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: 882030

Other (OTH) AF: 0.00 AC: 0 AN: 49046

⚠️ 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 v4.3

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;