18-49881833-C-T

Variant names:

• chr18-49881833-C-T
• rs1787566
• NM_001080467.3:c.3046-1378G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080467.3(MYO5B):​c.3046-1378G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 151,242 control chromosomes in the GnomAD database, including 54,482 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.85 (54482 hom., cov: 29)
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.449
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5B	NM_001080467.3	c.3046-1378G>A		intron_variant	Intron 22 of 39	ENST00000285039.12	NP_001073936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO5B	ENST00000285039.12	c.3046-1378G>A		intron_variant	Intron 22 of 39	1	NM_001080467.3	ENSP00000285039.6
MYO5B	ENST00000697219.1	c.2842-1378G>A		intron_variant	Intron 20 of 37			ENSP00000513188.1
MYO5B	ENST00000324581.10	c.475-1378G>A		intron_variant	Intron 2 of 18	2		ENSP00000315531.7

Frequencies

GnomAD3 genomes AF: 0.848 AC: 128170 AN: 151134 Hom.: 54431 Cov.: 29

Gnomad AFR AF: 0.872

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.890

Gnomad ASJ AF: 0.864

Gnomad EAS AF: 0.955

Gnomad SAS AF: 0.907

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.882

Gnomad NFE AF: 0.815

Gnomad OTH AF: 0.865

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.848 AC: 128275 AN: 151242 Hom.: 54482 Cov.: 29 AF XY: 0.853 AC XY: 62903 AN XY: 73754

African (AFR) AF: 0.873 AC: 35950 AN: 41198

American (AMR) AF: 0.890 AC: 13562 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.864 AC: 2997 AN: 3468

East Asian (EAS) AF: 0.954 AC: 4919 AN: 5154

South Asian (SAS) AF: 0.907 AC: 4366 AN: 4814

European-Finnish (FIN) AF: 0.809 AC: 8215 AN: 10158

Middle Eastern (MID) AF: 0.890 AC: 260 AN: 292

European-Non Finnish (NFE) AF: 0.815 AC: 55337 AN: 67900

Other (OTH) AF: 0.865 AC: 1819 AN: 2104

Alfa AF: 0.829 Hom.: 26022

Bravo AF: 0.855

Asia WGS AF: 0.933 AC: 3223 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.8
DANN	Benign	0.43
PhyloP100		0.45
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

dbSNP: rs1787566; hg19: chr18-47408203;