18-49929610-GAAAAAAA-GAAAAAA

Variant names:

• chr18-49929610-GA-G
• rs56278513
• NM_001080467.3:c.2004-13delT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001080467.3(MYO5B):​c.2004-13delT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.89 (52214 hom., cov: 0)
  • Exomes 𝑓: 0.51 (18740 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.06
• 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 -16 ACMG points.

• BP6: Variant 18-49929610-GA-G is Benign according to our data. Variant chr18-49929610-GA-G is described in ClinVar as Benign. ClinVar VariationId is 327057.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.959 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.2004-13delT		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.2004-13delT		intron	N/A	ENSP00000285039.6
	MYO5B	ENST00000697219.1		c.1800-13delT		intron	N/A	ENSP00000513188.1

Frequencies

GnomAD3 genomes AF: 0.890 AC: 118235 AN: 132892 Hom.: 52229 Cov.: 0

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.914

Gnomad ASJ AF: 0.933

Gnomad EAS AF: 0.983

Gnomad SAS AF: 0.954

Gnomad FIN AF: 0.848

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.882

Gnomad OTH AF: 0.903

GnomAD2 exomes AF: 0.479 AC: 54808 AN: 114366 AF XY: 0.479

Gnomad AFR exome AF: 0.475

Gnomad AMR exome AF: 0.484

Gnomad ASJ exome AF: 0.486

Gnomad EAS exome AF: 0.483

Gnomad FIN exome AF: 0.464

Gnomad NFE exome AF: 0.477

Gnomad OTH exome AF: 0.484

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.505 AC: 582046 AN: 1151828 Hom.: 18740 Cov.: 0 AF XY: 0.505 AC XY: 290457 AN XY: 575726

African (AFR) AF: 0.496 AC: 13138 AN: 26488

American (AMR) AF: 0.487 AC: 15578 AN: 31980

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 11134 AN: 22194

East Asian (EAS) AF: 0.500 AC: 16767 AN: 33528

South Asian (SAS) AF: 0.501 AC: 35155 AN: 70236

European-Finnish (FIN) AF: 0.488 AC: 17539 AN: 35970

Middle Eastern (MID) AF: 0.515 AC: 1812 AN: 3516

European-Non Finnish (NFE) AF: 0.508 AC: 446284 AN: 879040

Other (OTH) AF: 0.504 AC: 24639 AN: 48876

GnomAD4 genome AF: 0.890 AC: 118210 AN: 132874 Hom.: 52214 Cov.: 0 AF XY: 0.892 AC XY: 56607 AN XY: 63472

African (AFR) AF: 0.876 AC: 31078 AN: 35464

American (AMR) AF: 0.914 AC: 12010 AN: 13138

Ashkenazi Jewish (ASJ) AF: 0.933 AC: 3028 AN: 3244

East Asian (EAS) AF: 0.983 AC: 4529 AN: 4608

South Asian (SAS) AF: 0.954 AC: 3872 AN: 4058

European-Finnish (FIN) AF: 0.848 AC: 5863 AN: 6914

Middle Eastern (MID) AF: 0.930 AC: 240 AN: 258

European-Non Finnish (NFE) AF: 0.882 AC: 55170 AN: 62538

Other (OTH) AF: 0.904 AC: 1639 AN: 1814

Alfa AF: 0.448 Hom.: 142

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Diarrhea with Microvillus Atrophy Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1
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: rs56278513; hg19: chr18-47455980;