18-50147891-T-C

Variant names:

• chr18-50147891-T-C
• rs1985467
• NM_001080467.3:c.27+46876A>G

Variant summary

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

The NM_001080467.3(MYO5B):​c.27+46876A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 151,924 control chromosomes in the GnomAD database, including 9,855 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 0.35 (9855 hom., cov: 31)
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5B	NM_001080467.3	c.27+46876A>G		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.27+46876A>G		intron_variant	Intron 1 of 39	1	NM_001080467.3	ENSP00000285039.6
MYO5B	ENST00000697221.1	n.398+46876A>G		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53008 AN: 151806 Hom.: 9861 Cov.: 31

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.349 AC: 53013 AN: 151924 Hom.: 9855 Cov.: 31 AF XY: 0.344 AC XY: 25569 AN XY: 74252

African (AFR) AF: 0.250 AC: 10352 AN: 41422

American (AMR) AF: 0.311 AC: 4752 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1403 AN: 3466

East Asian (EAS) AF: 0.254 AC: 1307 AN: 5148

South Asian (SAS) AF: 0.236 AC: 1133 AN: 4804

European-Finnish (FIN) AF: 0.353 AC: 3730 AN: 10558

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.430 AC: 29240 AN: 67942

Other (OTH) AF: 0.346 AC: 729 AN: 2104

Alfa AF: 0.378 Hom.: 5727

Bravo AF: 0.338

Asia WGS AF: 0.232 AC: 807 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.57
DANN	Benign	0.73
PhyloP100		-1.0
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: rs1985467; hg19: chr18-47674261;