18-49916759-G-T

Variant names:

• chr18-49916759-G-T
• rs1217617
• NM_001080467.3:c.2091-4586C>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.2091-4586C>A 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 151,778 control chromosomes in the GnomAD database, including 26,006 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 (26006 hom., cov: 30)
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.253
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5B	NM_001080467.3	c.2091-4586C>A		intron_variant	Intron 17 of 39	ENST00000285039.12	NP_001073936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO5B	ENST00000285039.12	c.2091-4586C>A		intron_variant	Intron 17 of 39	1	NM_001080467.3	ENSP00000285039.6
MYO5B	ENST00000697219.1	c.1887-4586C>A		intron_variant	Intron 15 of 37			ENSP00000513188.1

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88327 AN: 151660 Hom.: 26003 Cov.: 30

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.779

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.623

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

GnomAD4 genome AF: 0.582 AC: 88366 AN: 151778 Hom.: 26006 Cov.: 30 AF XY: 0.582 AC XY: 43185 AN XY: 74164

African (AFR) AF: 0.489 AC: 20225 AN: 41340

American (AMR) AF: 0.653 AC: 9965 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2356 AN: 3470

East Asian (EAS) AF: 0.563 AC: 2889 AN: 5130

South Asian (SAS) AF: 0.566 AC: 2713 AN: 4792

European-Finnish (FIN) AF: 0.549 AC: 5800 AN: 10572

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.622 AC: 42208 AN: 67898

Other (OTH) AF: 0.620 AC: 1303 AN: 2102

Alfa AF: 0.599 Hom.: 3375

Bravo AF: 0.590

Asia WGS AF: 0.572 AC: 1987 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.69
PhyloP100		0.25
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: rs1217617; hg19: chr18-47443129;