chr18-49930071-A-G

Variant names:

• chr18-49930071-A-G
• rs1623892
• NM_001080467.3:c.2004-473T>C

Variant summary

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

The NM_001080467.3(MYO5B):​c.2004-473T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 152,058 control chromosomes in the GnomAD database, including 18,671 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 0.49 (18671 hom., cov: 32)
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.210
• Publications: 6 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.556 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.2004-473T>C		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.2004-473T>C		intron	N/A	ENSP00000285039.6
	MYO5B	ENST00000697219.1		c.1800-473T>C		intron	N/A	ENSP00000513188.1

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73807 AN: 151940 Hom.: 18669 Cov.: 32

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.728

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.486 AC: 73830 AN: 152058 Hom.: 18671 Cov.: 32 AF XY: 0.480 AC XY: 35668 AN XY: 74336

African (AFR) AF: 0.423 AC: 17527 AN: 41470

American (AMR) AF: 0.385 AC: 5883 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2037 AN: 3470

East Asian (EAS) AF: 0.224 AC: 1160 AN: 5172

South Asian (SAS) AF: 0.460 AC: 2215 AN: 4818

European-Finnish (FIN) AF: 0.472 AC: 4984 AN: 10570

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.561 AC: 38137 AN: 67972

Other (OTH) AF: 0.502 AC: 1056 AN: 2104

Alfa AF: 0.530 Hom.: 12197

Bravo AF: 0.472

Asia WGS AF: 0.371 AC: 1292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.72
DANN	Benign	0.70
PhyloP100		-0.21
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: rs1623892; hg19: chr18-47456441;