18-49941119-G-T

Variant names:

• chr18-49941119-G-T
• rs1787603
• NM_001080467.3:c.1753-3722C>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.1753-3722C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 151,974 control chromosomes in the GnomAD database, including 26,531 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 0.59 (26531 hom., cov: 31)
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 2 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 (AFR) allele frequency at 95% confidence interval = 0.643 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5B	NM_001080467.3	MANE Select	c.1753-3722C>A		intron	N/A	NP_001073936.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5B	ENST00000285039.12	TSL:1 MANE Select	c.1753-3722C>A		intron	N/A	ENSP00000285039.6
	MYO5B	ENST00000697219.1		c.1549-3722C>A		intron	N/A	ENSP00000513188.1
	MYO5B	ENST00000908785.1		c.1753-3722C>A		intron	N/A	ENSP00000578844.1

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88872 AN: 151854 Hom.: 26515 Cov.: 31

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.605

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

GnomAD4 genome AF: 0.585 AC: 88938 AN: 151974 Hom.: 26531 Cov.: 31 AF XY: 0.576 AC XY: 42766 AN XY: 74256

African (AFR) AF: 0.649 AC: 26908 AN: 41446

American (AMR) AF: 0.531 AC: 8112 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 2219 AN: 3468

East Asian (EAS) AF: 0.286 AC: 1477 AN: 5158

South Asian (SAS) AF: 0.480 AC: 2311 AN: 4810

European-Finnish (FIN) AF: 0.492 AC: 5178 AN: 10524

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.599 AC: 40684 AN: 67958

Other (OTH) AF: 0.605 AC: 1278 AN: 2114

Alfa AF: 0.491 Hom.: 2251

Bravo AF: 0.592

Asia WGS AF: 0.423 AC: 1469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.26
DANN	Benign	0.58
PhyloP100		-1.3
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: rs1787603; hg19: chr18-47467489;