18-49886819-C-T

Variant names:

• chr18-49886819-C-T
• rs1787606
• NM_001080467.3:c.3046-6364G>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.3046-6364G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 151,766 control chromosomes in the GnomAD database, including 25,778 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 0.58 (25778 hom., cov: 30)
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

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.3046-6364G>A		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.3046-6364G>A		intron	N/A	ENSP00000285039.6	Q9ULV0-1
	MYO5B	ENST00000697219.1		c.2842-6364G>A		intron	N/A	ENSP00000513188.1	A0A8V8TM52
	MYO5B	ENST00000908785.1		c.3046-6364G>A		intron	N/A	ENSP00000578844.1

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88143 AN: 151648 Hom.: 25770 Cov.: 30

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.622

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

GnomAD4 genome AF: 0.581 AC: 88191 AN: 151766 Hom.: 25778 Cov.: 30 AF XY: 0.581 AC XY: 43033 AN XY: 74120

African (AFR) AF: 0.511 AC: 21114 AN: 41354

American (AMR) AF: 0.632 AC: 9627 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 2255 AN: 3464

East Asian (EAS) AF: 0.536 AC: 2757 AN: 5140

South Asian (SAS) AF: 0.562 AC: 2689 AN: 4786

European-Finnish (FIN) AF: 0.545 AC: 5749 AN: 10544

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.616 AC: 41828 AN: 67924

Other (OTH) AF: 0.620 AC: 1304 AN: 2104

Alfa AF: 0.594 Hom.: 4653

Bravo AF: 0.587

Asia WGS AF: 0.563 AC: 1958 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.2
DANN	Benign	0.81
PhyloP100		0.18
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: rs1787606; hg19: chr18-47413189;