18-49851183-G-T

Position:

• chr18-49851183-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080467.3(MYO5B):​c.4222-1523C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 152,186 control chromosomes in the GnomAD database, including 54,836 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 0.85 (54834 hom., cov: 32)
  • Exomes 𝑓: 1.0 (2 hom.)
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO5B	NM_001080467.3	c.4222-1523C>A		intron_variant		ENST00000285039.12	NP_001073936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO5B	ENST00000285039.12	c.4222-1523C>A		intron_variant		1	NM_001080467.3	ENSP00000285039.6

Frequencies

GnomAD3 genomes AF: 0.848 AC: 128978 AN: 152064 Hom.: 54782 Cov.: 32

Gnomad AFR AF: 0.872

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.892

Gnomad ASJ AF: 0.866

Gnomad EAS AF: 0.957

Gnomad SAS AF: 0.911

Gnomad FIN AF: 0.803

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.815

Gnomad OTH AF: 0.867

GnomAD4 exome AF: 1.00 AC: 4 AN: 4 Hom.: 2 AF XY: 1.00 AC XY: 4 AN XY: 4

Gnomad4 AMR exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.848 AC: 129089 AN: 152182 Hom.: 54834 Cov.: 32 AF XY: 0.852 AC XY: 63409 AN XY: 74386

Gnomad4 AFR AF: 0.872

Gnomad4 AMR AF: 0.892

Gnomad4 ASJ AF: 0.866

Gnomad4 EAS AF: 0.957

Gnomad4 SAS AF: 0.912

Gnomad4 FIN AF: 0.803

Gnomad4 NFE AF: 0.815

Gnomad4 OTH AF: 0.866

Alfa AF: 0.824 Hom.: 20131

Bravo AF: 0.856

Asia WGS AF: 0.935 AC: 3252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.24
DANN	Benign	0.83

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

Publications

LitVar

Other links and lift over

dbSNP: rs546341; hg19: chr18-47377553;