chr18-49898744-T-C

Variant names:

• chr18-49898744-T-C
• rs1787292
• NM_001080467.3:c.2812-3570A>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.2812-3570A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 151,954 control chromosomes in the GnomAD database, including 25,932 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 (25932 hom., cov: 32)
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.558
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.625 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.2812-3570A>G		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.2812-3570A>G		intron	N/A	ENSP00000285039.6
	MYO5B	ENST00000697219.1		c.2608-3570A>G		intron	N/A	ENSP00000513188.1
	MYO5B	ENST00000324581.10	TSL:2	c.241-3570A>G		intron	N/A	ENSP00000315531.7

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88416 AN: 151836 Hom.: 25924 Cov.: 32

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.666

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.582 AC: 88464 AN: 151954 Hom.: 25932 Cov.: 32 AF XY: 0.582 AC XY: 43190 AN XY: 74244

African (AFR) AF: 0.500 AC: 20712 AN: 41404

American (AMR) AF: 0.636 AC: 9705 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2370 AN: 3472

East Asian (EAS) AF: 0.549 AC: 2833 AN: 5162

South Asian (SAS) AF: 0.567 AC: 2729 AN: 4814

European-Finnish (FIN) AF: 0.548 AC: 5791 AN: 10560

Middle Eastern (MID) AF: 0.671 AC: 196 AN: 292

European-Non Finnish (NFE) AF: 0.620 AC: 42154 AN: 67970

Other (OTH) AF: 0.619 AC: 1303 AN: 2106

Alfa AF: 0.601 Hom.: 4839

Bravo AF: 0.588

Asia WGS AF: 0.562 AC: 1956 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.1
DANN	Benign	0.72
PhyloP100		0.56
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: rs1787292; hg19: chr18-47425114;