rs2292382

Variant names:

• chr18-50098567-G-T
• rs2292382
• NM_001080467.3:c.28-43189C>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.28-43189C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,178 control chromosomes in the GnomAD database, including 1,352 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 0.13 (1352 hom., cov: 33)
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590
• Publications: 5 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

ENSG00000267591 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5B	NM_001080467.3	c.28-43189C>A		intron_variant	Intron 1 of 39	ENST00000285039.12	NP_001073936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO5B	ENST00000285039.12	c.28-43189C>A		intron_variant	Intron 1 of 39	1	NM_001080467.3	ENSP00000285039.6
MYO5B	ENST00000697221.1	n.399-43189C>A		intron_variant	Intron 1 of 4
ENSG00000267591	ENST00000587055.1	n.-175G>T		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19642 AN: 152060 Hom.: 1341 Cov.: 33

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.129 AC: 19697 AN: 152178 Hom.: 1352 Cov.: 33 AF XY: 0.130 AC XY: 9665 AN XY: 74398

African (AFR) AF: 0.132 AC: 5497 AN: 41506

American (AMR) AF: 0.108 AC: 1649 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 358 AN: 3472

East Asian (EAS) AF: 0.230 AC: 1193 AN: 5180

South Asian (SAS) AF: 0.218 AC: 1048 AN: 4812

European-Finnish (FIN) AF: 0.100 AC: 1061 AN: 10588

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8466 AN: 67998

Other (OTH) AF: 0.124 AC: 263 AN: 2116

Alfa AF: 0.132 Hom.: 822

Bravo AF: 0.128

Asia WGS AF: 0.243 AC: 848 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.69
PhyloP100		-0.059
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: rs2292382; hg19: chr18-47624937;