chr18-50123823-G-A

Variant names:

• chr18-50123823-G-A
• rs1705533
• NM_001080467.3:c.28-68445C>T

Variant summary

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

The NM_001080467.3(MYO5B):​c.28-68445C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 152,032 control chromosomes in the GnomAD database, including 28,674 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 0.61 (28674 hom., cov: 32)
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.878
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5B	NM_001080467.3	c.28-68445C>T		intron_variant	Intron 1 of 39	ENST00000285039.12	NP_001073936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO5B	ENST00000285039.12	c.28-68445C>T		intron_variant	Intron 1 of 39	1	NM_001080467.3	ENSP00000285039.6
MYO5B	ENST00000697221.1	n.399-68445C>T		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93097 AN: 151914 Hom.: 28654 Cov.: 32

Gnomad AFR AF: 0.613

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.636

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.632

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

GnomAD4 genome AF: 0.613 AC: 93161 AN: 152032 Hom.: 28674 Cov.: 32 AF XY: 0.614 AC XY: 45615 AN XY: 74332

African (AFR) AF: 0.613 AC: 25398 AN: 41460

American (AMR) AF: 0.694 AC: 10610 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2132 AN: 3472

East Asian (EAS) AF: 0.636 AC: 3289 AN: 5172

South Asian (SAS) AF: 0.647 AC: 3118 AN: 4816

European-Finnish (FIN) AF: 0.567 AC: 5989 AN: 10570

Middle Eastern (MID) AF: 0.582 AC: 170 AN: 292

European-Non Finnish (NFE) AF: 0.596 AC: 40493 AN: 67938

Other (OTH) AF: 0.632 AC: 1333 AN: 2110

Alfa AF: 0.606 Hom.: 82509

Bravo AF: 0.621

Asia WGS AF: 0.678 AC: 2356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.12
DANN	Benign	0.51
PhyloP100		-0.88
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: rs1705533; hg19: chr18-47650193;